The reasons for the formation of atherosclerosis are diverse and complex,and atherosclerosis as a kind of systemic disease has the characteristics of focal selectivity,which occurs in the carotid bifurcation.The featu...The reasons for the formation of atherosclerosis are diverse and complex,and atherosclerosis as a kind of systemic disease has the characteristics of focal selectivity,which occurs in the carotid bifurcation.The feature enables a large number of studies have found that the severe local hemodynamic characteristics has a great influence to the occurrence of this disease.This paper briefly reviews the related research on the local hemodynamics of carotid bifurcation.The relevant parameters of local hemodynamics were sorted out and summarized,and the effects of wall shear force and its derived parameters on the generation,progression and rupture of carotid atherosclerosis and their clinical applications were reviewed,in order to provide mechanical information for the early warning of carotid plaque rupture.At the same time,this paper describes the transformation of local hemodynamics research in the clinical application of carotid atherosclerosis disease,in order to provide personalized selection and basis for the clinical treatment of this disease.展开更多
Background:The expression of pyruvate kinase muscle 2(PKM2)is augmented in macrophages of patients with atherosclerotic coronary artery disease.The role of PKM2 in atherosclerosis is to be determined.Methods:Global an...Background:The expression of pyruvate kinase muscle 2(PKM2)is augmented in macrophages of patients with atherosclerotic coronary artery disease.The role of PKM2 in atherosclerosis is to be determined.Methods:Global and myeloid cell-specific PKM2 knock-in mice with ApoE^(-/-)background(ApoE^(-/-),PKM2^(KI/KI)and Lyz2-cre,ApoE^(-/-),and PKM2^(flox/flox))were produced to evaluate the clinical significance of PKM2 in atherosclerosis development.Wild-type and PKM2 knock-in macrophages were isolated to assess the function of PKM2 in macrophage phagocytosis.Atherosclerotic mice were treated with PKM2 inhibitor shikonin(SKN)to evaluate the therapeutic potential of PKM2 suppression in atherosclerosis.Results:Oxidized low-density lipoprotein(oxLDL)upregulated PKM2 in macrophages.PKM2 in return promoted the uptake of oxLDL by macrophages.Overexpressed PKM2 accelerated atherosclerosis in mice.SKN blocked the progress of mouse atherosclerosis.Conclusions:PKM2 accelerates macrophage phagocytosis and atherosclerosis.Targeting PKM2 is a potential therapy for atherosclerosis.展开更多
BACKGROUND Ischemic gastritis is a clinically rare disease with high mortality that infrequently reported in the medical literature and under-recognized clinically and histopatho-logically.Early diagnosis and treatmen...BACKGROUND Ischemic gastritis is a clinically rare disease with high mortality that infrequently reported in the medical literature and under-recognized clinically and histopatho-logically.Early diagnosis and treatment can only be achieved through upper gastrointestinal endoscopy after symptoms appear.CASE SUMMARY A 68-year-old woman with a history of intracranial aneurysm developed dizziness,chest tightness and unconsciousness for 2 d.Computed tomography angiography showed diffuse coronary atherosclerosis,moderate to severe stenosis in the proximal end of the left anterior descending branch,multiple calcified plaques in the proximal end of the circumflex branch and right coronary artery,and mild to moderate stenosis.The patient also developed diffuse atherosclerosis in the splenic and mesenteric arteries,with mild lumen stenosis and athero-sclerosis in the abdominal aorta and its branches.Endoscopy showed submucosal congestion and damage of the entire gastric mucosa,of which the fundus and body of the stomach were most seriously affected.The mucosa was swollen,with a deep purple color,surface erosion and dark red oozing blood.Pathological examination showed bleeding and necrosis of the gastric mucosa,with residual contours of the gastric glands,consistent with ischemic gastritis.CONCLUSION Ischemic gastritis is a rare disease that may be difficult to diagnose as its symptoms may be similar to those of other gastrointestinal diseases.Diagnosis is usually based on endoscopic and pathological examinations,which show insufficient blood supply to the gastric mucosa leading to mucosal damage and necrosis.展开更多
In medical science for envisaging human body’s phenomenal structure a major part has been driven by image processing techniques.Major objective of this work is to detect of cerebral atherosclerosis for image segmenta...In medical science for envisaging human body’s phenomenal structure a major part has been driven by image processing techniques.Major objective of this work is to detect of cerebral atherosclerosis for image segmentation applica-tion.Detection of some abnormal structures in human body has become a difficult task to complete with some simple images.For expounding and distinguishing neural architecture of human brain in an effective manner,MRI(Magnetic Reso-nance Imaging)is one of the most suitable and significant technique.Here we work on detection of Cerebral Atherosclerosis from MRI images of patients.Cer-ebral Atherosclerosis is a cerebral vascular disease causes narrowing of the arteries due to buildup of fatty plaque inside the blood vessels of the brain.It leads to Ischemic stroke if not diagnosed early.Stroke affects majorly old age people and percentage of affected women is more compared to men.Results:Preproces-sing is done by using alpha trimmed meanfilter which is used to remove noise and also it enhances the image.Segmentation of cerebral atherosclerosis is done by using K-means clustering,Contextual clustering,and proposed Hybrid algo-rithm.Various parameters like Correlation,Pixel density,energy is determined and from the analysis of parameters it is determined that proposed Hybrid algo-rithm is efficient.展开更多
Background and Purpose: Thrombotic disease is a leading cause of death in industrialized countries. The development of atherosclerosis is a major underlying pathogenesis. Atherosclerotic lesions are largely related to...Background and Purpose: Thrombotic disease is a leading cause of death in industrialized countries. The development of atherosclerosis is a major underlying pathogenesis. Atherosclerotic lesions are largely related to abnormalities in lipid metabolism, and improvement of dietary habits is of great significance. Chlorella is a unicellular organism belonging to the green algae family, and is consumed worldwide as a functional food for the purpose of health promotion due to its excellent nutritional balance including high quality protein. In this study, we investigated the effects of long-term consumption of Chlorella as a food on the development of atherosclerosis and its ability to dissolve thrombi caused by the disruption of the atherosclerotic layer as a functional study of Chlorella. Methods: ApoE<sup>−/−</sup> and Ldlr<sup>−/−</sup> double-knockout mice were fed a chlorella-supplemented experimental diet for 14 weeks. The Entire aorta method was used to measure atherosclerosis development, and the area of sclerotic vessels was evaluated as a percentage of the total area of vessels. In addition, mRNA levels of lipid metabolism-related proteins in the liver and blood vessels were analyzed, as well as blood lipoprotein analysis. Spontaneous thrombolytic activity was measured by measuring the change in volume over time of thrombus formed in microvessel running over the cremaster muscle of the mice using the He-Ne laser-induced thrombus model. Results: There was no significant difference between the two groups in atherosclerosis development compared to the placebo group. However, a significant decrease in SREBP-1 mRNA level and a significant increase in mRNA levels of LXR and CPY71a were observed in the chlorella group. Cholesterol and TG levels in each lipoprotein fraction did not differ between the two groups. On the other hand, thrombolysis in vivo was not significantly different between the two groups in terms of thrombus volume at 60 minutes after thrombus formation. However, a trend toward decreased PAI-1 and TAFI mRNA expression levels was observed in the chlorella group. Conclusion: Intake of chlorella as a food suggested an effect on cholesterol catabolism, increased bile acid synthesis, improved lipid metabolism, and inhibited the development of atherosclerosis. Furthermore, it was suggested that chlorella may suppress the expression of fibrinolytic inhibitory factor and enhance thrombolytic activity.展开更多
Objective: To investigate the correlation between fundus atherosclerosis and carotid arterial atherosclerosis. Methods: A total of 516 people undergoing physical examination in Deyang People’s Hospital between June 2...Objective: To investigate the correlation between fundus atherosclerosis and carotid arterial atherosclerosis. Methods: A total of 516 people undergoing physical examination in Deyang People’s Hospital between June 2020 and December 2022 were randomly selected. Fundus atherosclerosis and carotid arterial atherosclerosis were evaluated by fundus photography and carotid artery ultrasonography, respectively. Results: Among the 516 physical examination patients, 198 (38.4%) had normal fundus examination, and 318 (61.6%) had fundus arteriosclerosis. Among them, 166 cases were of grade I (32.2%), 86 cases were of grade II (16.7%), and 66 cases were of grade III (12.8%). There were 286 cases (55.4%) without carotid atherosclerosis, 201 cases (38.9%) with carotid atherosclerotic plaque, and 33 cases (6.4%) with carotid stenosis. Fundus arteriosclerosis is independently associated with carotid artery intima-media thickness, vulnerable plaques, plaque scores, and carotid artery stenosis (P Conclusion: In summary, there is a close relationship between carotid artery disease and the degree of arteriosclerosis in the eyeground. Fundus photography is a simple, non-invasive, and easily acceptable method of inspection. The results obtained from it are useful in determining the severity of carotid atherosclerosis and guiding early detection and intervention in clinical cases. This can help reduce the incidence of cardiovascular and cerebrovascular diseases.展开更多
Calpains are calcium-activated cysteine proteases. There are two main isoforms of calpain that are ubiquitously expressed in tissues, calpain μ or calpain 1, which requires micromolar Ca<sup>2+</sup> for ...Calpains are calcium-activated cysteine proteases. There are two main isoforms of calpain that are ubiquitously expressed in tissues, calpain μ or calpain 1, which requires micromolar Ca<sup>2+</sup> for activation, and calpain or 2, which requires millimolar Ca<sup>2+</sup> for activation. The presence of other calpains is tissue specific. Atherosclerosis (AS) is an important risk factor for cerebral infarction, coronary heart disease and peripheral vascular disease. It was originally thought that AS was caused by impaired lipid metabolism. This research briefly reviewed Calpain Family, the structure and activation mechanism of calpain1, Calpains in the pathogenesis of atherosclerosis, NLRP3 structural characteristics and activation, ROS/NLRP3 inflammasome activation mechanism and ROS/NLRP3 inflammasome in atherosclerosis. The research showed that the Calpain-1 may play an important role in mitochondrial ROS/NLRP3 inflammasome in atherosclerosis.展开更多
Background:Naodesheng tablets(NDST)was widely used in clinical treatment as a drug for cardiovascular diseases,but the mechanism for treating atherosclerosis was unknown.On the basis of network pharmacology and bioinf...Background:Naodesheng tablets(NDST)was widely used in clinical treatment as a drug for cardiovascular diseases,but the mechanism for treating atherosclerosis was unknown.On the basis of network pharmacology and bioinformatics,predict the relevant targets and signalling pathways for NDST in the treatment of atherosclerosis.Methods:First,the targets of NDST and the targets for treating atherosclerosis were looked for in different databases.Next,Venny 2.1.0 was used to find the genes that overlapped between NDST and targets for treating atherosclerosis.Subsequently,the herb-active ingredient-target-disease were obtained to explore the hub compound.Furthermore,the Metascape database was used for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis.And we constructed the“active ingredient-intersection target-pathway”network by Cytoscape software to gain the hub genes and pathways.Finally,molecular docking was used to verify the affinity of hub ingredients and hub genes.Results:In the results,67 active ingredients and 322 targets of NDST were selected in ingredients-targets network.154 overlapping targets of NDST(322)and atherosclerosis(1330)were obtained.Then,the herb-active ingredient-target-disease showed that quercetin,apigenin and luteolin were the hub ingredients to treat atherosclerosis.Further,the hub genes(PTGS2,RXRA,CASP3)and pathways(lipid and atherosclerosis)were accessed in active ingredient-intersection target-pathway.Finally,the results indicated that quercetin,apigenin and luteolin were better binding the PTGS2,RXRA,CASP3,especially PTGS2 and luteolin in molecular docking.Conclusion:In conclusion,quercetin,apigenin and luteolin,as the main ingredients of NDST could play a important role in PTGS2,RXRA,and CASP3 for treating atherosclerosis via the lipid and atherosclerosis(TNF signaling pathway).展开更多
The objective of this study was to investigate the main active ingredients,potential targets,and possible mechanisms of action of the combination of Radix Astragali and Caulis Spatholobi for the treatment of atheroscl...The objective of this study was to investigate the main active ingredients,potential targets,and possible mechanisms of action of the combination of Radix Astragali and Caulis Spatholobi for the treatment of atherosclerosis using network pharmacology.The study aimed to provide a reference basis for the development of new formulations and clinical use of Chinese medicine.The main components of Radix Astragali and Caulis Spatholobi were obtained from the TCMSP,BATMAN-TCM database,and literature reports.The targets corresponding to the main components were imported into the Uniprot database to standardize the names,and target information was supplemented with the Swiss Target Prediction database.Disease-related targets were obtained from DrugBank,OMIM,CTD,GeneCards,and DisGeNET online databases.Venn tools were used to obtain the potential targets of Radix Astragali and Caulis Spatholobi for the treatment of AS.The intersecting genes were imported into the STRING 11.5 database to construct protein-protein interaction network maps and analyze their interactions.Cytoscape 3.7.1 software was used to mine their core targets.GO function and KEGG signaling pathway enrichment analysis were performed using the DAVID v2023q1 database.The results were imported into the“Bioinformatics Cloud Platform”to generate enrichment bubble maps.Finally,the“component-target-pathway”diagram was constructed using Cytoscape 3.7.1 software.The study found that 78 major active ingredients and 527 potential targets were obtained from Radix Astragali and Caulis Spatholobi.The main active components of the two in combination for the treatment of AS are quercetin,stigmasterol,kaempferol,luteolin,formononetin,etc.The key targets involve CDKN1A,E2F1,CDK4,CDK2,CDK1,RB1,TP53,CDKN1B,IL6,JUN,etc.The main pathways involved the AGE-RAGE signaling pathway in diabetic complications,cancer pathway,etc.The biological processes involved include positive regulation of gene expression,negative regulation of apoptotic process,etc.The study initially verified the feasibility of the combination of Radix Astragali-Caulis Spatholobi by Qi-invigorating(promoting human metabolic activity)and blood-activating for the treatment of AS.It demonstrated that the combination of Chinese medicine has multi-level,multi-target,and multi-pathway mechanisms of action to treat the disease,providing a reference basis for the development and utilization of new drugs.展开更多
Background:The present study intented to delve into the molecular mechanism of Cordyceps sinensis(C.sinensis)in treating atherosclerosis by combining network pharmacology and molecular docking analysis.Methods:We sear...Background:The present study intented to delve into the molecular mechanism of Cordyceps sinensis(C.sinensis)in treating atherosclerosis by combining network pharmacology and molecular docking analysis.Methods:We searched the databases including Traditional Chinese Medicines Systems Pharmacology Database and Analysis Platform,PubChem,and PharmMapper to screen out the active chemical ingredients of C.sinensis and the corresponding targets.The String database was used for the matching normalization of results,and the software Cytoscape 3.7.2 was adopted to establish the C.sinensis-active components-targets of action-disease network.The databases of Online Mendelian Inheritance in Man database,GeneCards,Therapeutic Target Database,and DisGNET were searched to yield the major targets of atherosclerosis(AS),which were matched with the active component targets of C.sinensis to identify the potential therapeutic targets.The String database was utilized to set up the protein-protein interaction network,and Cytoscape software was applied for topological analysis,which was followed by the Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes signaling pathway analysis based on the DAVID database.Finally,the core components of C.sinensis and the targets of action were confirmed via molecular docking on AutoDock Vina and PyMOL.Results:In total,7 bioactive ingredients of C.sinensis were identified from Traditional Chinese Medicines Systems Pharmacology Database and Analysis Platform database and 319 predicted targets were obtained,231 of which were associated with AS.The core targets involved in AS treatment with C.sinensis included MAPK1,SRC,PIK3R1,AKT1,and HSP90AA1.The enrichment analysis unveiled the primary pathways involved in these processes,such as pathways in cancer and lipid and atherosclerosis.Moreover,through molecular docking,it was found that the active ingredients of C.sinensis presented with strong binding capacities with their corresponding targets,and the strongest binding capacity was observed between peroxyergosterol and SRC.Conclusions:The present study revealed at the molecular level that C.sinensis played its role in AS treatment through multiple drug active components,targets of action and pathways,which would point out the direction and provide theoretic basis for future research.展开更多
Though a century old hypothesis, infection as a cause for atherosclerosis is still a debatable issue. Epidemiological and clinical studies had shown a possible association but inhomogeneity in the study population and...Though a century old hypothesis, infection as a cause for atherosclerosis is still a debatable issue. Epidemiological and clinical studies had shown a possible association but inhomogeneity in the study population and study methods along with potential confounders have yielded conflicting results. Infection triggers a chronic inflammatory state which along with other mechanisms such as dyslipidemia, hyper-homocysteinemia, hypercoagulability, impaired glucose metabolism and endothelial dysfunction, contribute in pathogenesis of atherosclerosis. Studies have shown a positive relations between Cytotoxic associated gene-A positive strains of Helicobacter pylori and vascular diseases such as coronary artery disease and stroke. Infection mediated genetic modulation is a new emerging theory in this regard. Further large scale studies on infection and atherosclerosis focusing on multiple pathogenetic mechanisms may help in refining our knowledge in this aspect.展开更多
Atherosclerosis is a chronic inflammatory disease associated with cardiovascular dysfunction including myocardial infarction, unstable angina, sudden cardiac death, stroke and peripheral thromboses. It has been predic...Atherosclerosis is a chronic inflammatory disease associated with cardiovascular dysfunction including myocardial infarction, unstable angina, sudden cardiac death, stroke and peripheral thromboses. It has been predicted that atherosclerosis will be the primary cause of death in the world by 2020. Atherogenesis is initiated by endothelial injury due to oxidative stress associated with cardiovascular risk factors including diabetes mellitus, hypertension, cigarette smoking, dyslipidemia, obesity, and metabolic syndrome. The impairment of the endothelium associated with cardiovascular risk factors creates an imbalance between vasodilating and vasoconstricting factors, in particular, an increase in angiotensin Ⅱ(Ang Ⅱ) and a decrease in nitric oxide. The renin-angiotensin system(RAS), and its primary mediator Ang Ⅱ, also have a direct influence on the progression of the atherosclerotic process via effects on endothelial function, inflammation, fibrinolytic balance, and plaque stability. Anti-inflammatory agents [statins, secretory phospholipase A2 inhibitor, lipoprotein-associated phospholipase A2 inhibitor, 5-lipoxygenase activating protein, chemokine motif ligand-2, C-C chemokine motif receptor 2 pathway inhibitors, methotrexate, IL-1 pathway inhibitor and RAS inhibitors(angiotensin-converting enzyme inhibitors)], Ang Ⅱ receptor blockers and ranin inhibitors may slow inflammatory processes and disease progression. Several studies in human using anti-inflammatory agents and RAS inhibitors revealed vascular benefits and reduced progression of coronary atherosclerosis in patients with stable angina pectoris; decreased vascular inflammatory markers, improved common carotid intima-media thickness and plaque volume in patients with diagnosed atherosclerosis. Recent preclinical studies have demonstrated therapeutic efficacy of vitamin D analogs paricalcitol in Apo E-deficient atherosclerotic mice.展开更多
Non-alcoholic fatty liver disease(NAFLD) represents the most common and emerging chronic liver disease worldwide. It includes a wide spectrum of liver diseasesranging from simple fatty liver to non-alcoholic steatohep...Non-alcoholic fatty liver disease(NAFLD) represents the most common and emerging chronic liver disease worldwide. It includes a wide spectrum of liver diseasesranging from simple fatty liver to non-alcoholic steatohepatitis(NASH),which may progress to fibrosis and more severe liver complications such as cirrhosis,hepatocellular carcinoma and liver mortality. NAFLD is strongly associated with obesity,insulin resistance,hypertension,and dyslipidaemia,and is now regarded as the liver manifestation of the metabolic syndrome. The increased mortality of patients with NAFLD is primarily a result of cardiovascular disease and,to a lesser extent,to liver related diseases. Increased oxidative stress has been reported in both patients with NAFLD and patient with cardiovascular risk factors. Thus,oxidative stress represents a shared pathophysiological disorder between the two conditions. Several therapeutic strategies targeting oxidative stress reduction in patients with NAFLD have been proposed,with conflicting results. In particular,vitamin E supplementation has been suggested for the treatment of non-diabetic,non-cirrhotic adults with active NASH,although this recommendation is based only on the results of a single randomized controlled trial. Other antioxidant treatments suggested are resveratrol,silybin,L-carnitine and pentoxiphylline. No trial so far,has evaluated the cardiovascular effects of antioxidant treatment in patients with NAFLD. New,large-scale studies including as end-point also the assessment of the atherosclerosis markers are needed.展开更多
Atherosclerotic cardiovascular diseases, chronic inflam-matory diseases of multifactorial etiology, are the lead-ing cause of death worldwide. In the last decade, more infectious agents, labeled as "infectious bu...Atherosclerotic cardiovascular diseases, chronic inflam-matory diseases of multifactorial etiology, are the lead-ing cause of death worldwide. In the last decade, more infectious agents, labeled as "infectious burden", rather than any single pathogen, have been showed to con-tribute to the development of atherosclerosis through different mechanisms. Some microorganisms, such as Chlamydia pneumoniae(C. pneumoniae), human cytomegalovirus, etc. may act directly on the arterial wall contributing to endothelial dysfunction, foam cell formation, smooth muscle cell proliferation, platelet ag-gregation as well as cytokine, reactive oxygen specie, growth factor, and cellular adhesion molecule produc-tion. Others, such as Helicobacter pylori(H. pylori), in-fluenza virus, etc. may induce a systemic inflammation which in turn may damage the vascular wall(e.g., by cytokines and proteases). Moreover, another indirect mechanism by which some infectious agents(such as H. pylori, C. pneumoniae, periodontal pathogens, etc.) may play a role in the pathogenesis of atherosclero-sis is molecular mimicry. Given the complexity of the mechanisms by which each microorganism may con-tribute to atherosclerosis, defining the interplay of moreinfectious agents is far more difficult because the pro-atherogenic effect of each pathogen might be ampli-fied. Clearly, continued research and a greater aware-ness will be helpful to improve our knowledge on the complex interaction between the infectious burden and atherosclerosis.展开更多
In this mini-review several commonly used animal models of atherosclerosis have been discussed.Among them,emphasis has been made on mice,rabbits,pigs and non-human primates.Although these animal models have played a s...In this mini-review several commonly used animal models of atherosclerosis have been discussed.Among them,emphasis has been made on mice,rabbits,pigs and non-human primates.Although these animal models have played a significant role in our understanding of induction of atherosclerotic lesions,we still lack a reliable animal model for regression of the disease.Researchers have reported several genetically modified and transgenic animal models that replicate human atherosclerosis,however each of current animal models have some limitations.Among these animal models,the apolipoprotein(apo) E-knockout(KO)mice have been used extensively because they develop spontaneous atherosclerosis.Furthermore,atherosclerotic lesions developed in this model depending on experimental design may resemble humans' stable and unstable atherosclerotic lesions.This mouse model of hypercholesterolemia and atherosclerosis has been also used to investigate the impact of oxidative stress and inflammation on atherogenesis.Low density lipoprotein(LDL)-r-KO mice are a model of human familial hypercholesterolemia.However,unlike apo E-KO mice,the LDL-r-KO mice do not develop spontaneous atherosclerosis.Both apo E-KO and LDL-r-KO mice have been employed to generate other relevant mouse models of cardiovascular disease through breeding strategies.In addition to mice,rabbits have been used extensively particularly to understand the mechanisms of cholesterol-induced atherosclerosis.The present review paper details the characteristics of animal models that are used in atherosclerosis research.展开更多
Despite all the therapeutic advances in the field of cardiology, cardiovascular diseases, and in particular coronary artery disease, remain the leading cause of death and disability worldwide, thereby underlining the ...Despite all the therapeutic advances in the field of cardiology, cardiovascular diseases, and in particular coronary artery disease, remain the leading cause of death and disability worldwide, thereby underlining the importance of acquiring new therapeutic options in this field. A reduction in elevated resting heart rate (HR) has long been postulated as a therapeutic approach in the management of cardiovascular disease. An increased HR has been shown to be associated with increased progression of coronary atherosclerosis in animal models and patients. A high HR has also been associated with a greatly increased risk of plaque rupture in patients with coronary atherosclerosis. Endothelial function may be an important link between HR and atherosclerosis. An increased HR has been shown experimentally to cause endothelial dysfunction. Inflammation plays a significant role in the pathogenesis and progression of atherosclerosis. In the literature, there is data that shows an association between HR and circulating markers of vascular inflammation. In addition, HR reduction by pharmacological intervention with ivabradine (a selective HR-lowering agent that acts by inhibiting the pacemaker ionic current If in sinoatrial node cells) reduces the formation of atherosclerotic plaques in animal models of lipid-induced atherosclerosis. The aim of this editorial is to review the possible role of ivabradine on atherosclerosis.展开更多
Mitochondrial physiology and biogenesis play a crucial role in the initiation and progression of cardiovascular disease following oxidative stress-induced damage such as atherosclerosis(AST).Dysfunctional mitochondria...Mitochondrial physiology and biogenesis play a crucial role in the initiation and progression of cardiovascular disease following oxidative stress-induced damage such as atherosclerosis(AST).Dysfunctional mitochondria caused by an increase in mitochondrial reactive oxygen species(ROS)production,accumulation of mitochondrial DNA damage,and respiratory chain deficiency induces death of endothelial/smooth muscle cells and favors plaque formation/rupture via the regulation of mitochondrial biogenesis-related genes such as peroxisome proliferator-activated receptorγcoactivator(PGC-1),although more detailed mechanisms still need further study.Based on the effect of healthy mitochondria produced by mitochondrial biogenesis on decreasing ROS-mediated cell death and the recent finding that the regulation of PGC-1 involves mitochon- drial fusion-related protein(mitofusin),we thus infer the regulatory role of mitochondrial fusion/fission balance in AST pathophysiology.In this review,the first section discusses the possible association between AST-inducing factors and the molecular regulatory mechanisms of mitochondrial biogenesis and dynamics,and explains the role of mitochondria-dependent regulation in cell apoptosis during AST development. Furthermore,nitric oxide has the Janus-faced effect by protecting vascular damage caused by AST while being a reactive nitrogen species(RNS)which act together with ROS to damage cells.Therefore,in the second section we discuss mitochondrial ATP-sensitive K+ channels,which regulate mitochondrial ion transport to maintain mitochondrial physiology,involved in the regulation of ROS/RNS production and their influence on AST/cardiovascular diseases(CVD).Through this review,we can further appreciate the multi-regulatory functions of the mitochondria involved in AST development.The understanding of these related mechanisms will benefit drug development in treating AST/CVD through targeted biofunctions of mitochondria.展开更多
Coronary heart disease is the single most common cause of illness and death in the developed world.Coronary atherosclerosis is by far the most frequent cause of ischemic heart disease,and plaque disruption with superi...Coronary heart disease is the single most common cause of illness and death in the developed world.Coronary atherosclerosis is by far the most frequent cause of ischemic heart disease,and plaque disruption with superimposed thrombosis is the main cause of the acute coronary syndromes of unstable angina,myocardial infarction,and sudden death.Atherosclerosis is the result of a complex interaction between blood elements,disturbed flow,and vessel wall abnormality,involving several pathological processes:inflammation,with increased endothelial permeability,endothelial activation,and monocyte recruitment;growth,with smooth muscle cell proliferation,migration,and matrix synthesis;degeneration,with lipid accumulation;necrosis,possibly related to the cytotoxic effect of oxidized lipid;calcification/ossification,which may represent an active rather than a dystrophic process;and thrombosis,with platelet recruitment and fibrin formation.In this review we discuss these processes and the possible pathological effects of Chlamydia infection and the ensuing phlogosis.展开更多
Mounting evidence supports that a newly identified regulatory T cell (Treg),CD4+LAP+ Treg,is associated with oral tolerance induction and following inhibition of atherosclerosis,but little is described about whether n...Mounting evidence supports that a newly identified regulatory T cell (Treg),CD4+LAP+ Treg,is associated with oral tolerance induction and following inhibition of atherosclerosis,but little is described about whether nasal tolerance to antigen likewise induces the novel Tregs production and the relevant antiatherosclerotic benefit.We investigated the effect of nasal administration of heat shock protein-60 (HSP60) on atherogenesis.HSP60 or phosphate buffer solution (PBS) was nasally adminis-tered to six-week-old male ApoE-/-mice.At the 10th week after the nasal administration,there was a significant decrease in atherosclerotic plaque areas of aortic roots in the HSP60-treated mice as com-pared with those in the PBS-treated mice.Atherosclerosis suppression was accompanied with a signifi-cant increase in CD4+LAP+ and CD4+CD25+Foxp3+ Tregs and a concurrently increased production of TGF-β in the HSP60-treated mice.The protective effect of HSP60 was offset by injection of anti-TGF-βantibody.It is concluded that nasal administration of HSP60 can inhibit atherosclerotic formation through immune tolerance which is established by Tregs depending on the induction of anti-inflammatory cytokine TGF-β.Immune tolerance induced by nasal administration of HSP60 may provide an alternative therapeutic method for atherosclerosis.展开更多
Hepatitis C virus(HCV)infection represents a major health issue worldwide due to its burden of chronic liver disease and extrahepatic manifestations including cardiovascular diseases,which are associated with excess m...Hepatitis C virus(HCV)infection represents a major health issue worldwide due to its burden of chronic liver disease and extrahepatic manifestations including cardiovascular diseases,which are associated with excess mortality.Analysis of published studies supports the view that HCV infection should be considered a risk factor for the development of carotid atherosclerosis,heart failure and stroke.In contrast,findings from studies addressing coronary artery disease and HCV have yielded conflicting results.Therefore,meta-analytic reviews and prospective studies are warranted.The pathogenic mechanisms connecting HCV infection,chronic liver disease,and atherogenesis are not completely understood.However,it has been hypothesized that HCV may promote atherogenesis and its complications through several direct and indirect biological mechanisms involving HCV colonization and replication within arterial walls,liver steatosis and fibrosis,enhanced and imbalanced secretion of inflammatory cytokines,oxidative stress,endotoxemia,mixed cryoglobulinemia,perturbed cellular and humoral immunity,hyperhomocysteinemia,hypo-adiponectinaemia,insulin resistance,type 2 diabetes and other components of the metabolic syndrome.Understanding these complex mechanisms is of fundamental importance for the development of novel therapeutic approaches to prevent and to treat vascular complications in patients with chronic HCV infection.Currently,it seems that HCV clearance by interferon and ribavirin treatment significantly reduces non-liver-related mortality;moreover,interferon-based treatment appears to decrease the risk of ischemic stroke.展开更多
基金Health Industry Scientific Research Project of Hainan Province(20A200219)。
文摘The reasons for the formation of atherosclerosis are diverse and complex,and atherosclerosis as a kind of systemic disease has the characteristics of focal selectivity,which occurs in the carotid bifurcation.The feature enables a large number of studies have found that the severe local hemodynamic characteristics has a great influence to the occurrence of this disease.This paper briefly reviews the related research on the local hemodynamics of carotid bifurcation.The relevant parameters of local hemodynamics were sorted out and summarized,and the effects of wall shear force and its derived parameters on the generation,progression and rupture of carotid atherosclerosis and their clinical applications were reviewed,in order to provide mechanical information for the early warning of carotid plaque rupture.At the same time,this paper describes the transformation of local hemodynamics research in the clinical application of carotid atherosclerosis disease,in order to provide personalized selection and basis for the clinical treatment of this disease.
基金National Key R&D program of China,Grant/Award Number:2021YFC2500700The National Natural Science Foundation of China+1 种基金Grant/Award Number:81730078The Chinese Academy of Medical Sciences Initiative for Innovative Medicine,Grant/Award Number:2021-I2M-1-049。
文摘Background:The expression of pyruvate kinase muscle 2(PKM2)is augmented in macrophages of patients with atherosclerotic coronary artery disease.The role of PKM2 in atherosclerosis is to be determined.Methods:Global and myeloid cell-specific PKM2 knock-in mice with ApoE^(-/-)background(ApoE^(-/-),PKM2^(KI/KI)and Lyz2-cre,ApoE^(-/-),and PKM2^(flox/flox))were produced to evaluate the clinical significance of PKM2 in atherosclerosis development.Wild-type and PKM2 knock-in macrophages were isolated to assess the function of PKM2 in macrophage phagocytosis.Atherosclerotic mice were treated with PKM2 inhibitor shikonin(SKN)to evaluate the therapeutic potential of PKM2 suppression in atherosclerosis.Results:Oxidized low-density lipoprotein(oxLDL)upregulated PKM2 in macrophages.PKM2 in return promoted the uptake of oxLDL by macrophages.Overexpressed PKM2 accelerated atherosclerosis in mice.SKN blocked the progress of mouse atherosclerosis.Conclusions:PKM2 accelerates macrophage phagocytosis and atherosclerosis.Targeting PKM2 is a potential therapy for atherosclerosis.
文摘BACKGROUND Ischemic gastritis is a clinically rare disease with high mortality that infrequently reported in the medical literature and under-recognized clinically and histopatho-logically.Early diagnosis and treatment can only be achieved through upper gastrointestinal endoscopy after symptoms appear.CASE SUMMARY A 68-year-old woman with a history of intracranial aneurysm developed dizziness,chest tightness and unconsciousness for 2 d.Computed tomography angiography showed diffuse coronary atherosclerosis,moderate to severe stenosis in the proximal end of the left anterior descending branch,multiple calcified plaques in the proximal end of the circumflex branch and right coronary artery,and mild to moderate stenosis.The patient also developed diffuse atherosclerosis in the splenic and mesenteric arteries,with mild lumen stenosis and athero-sclerosis in the abdominal aorta and its branches.Endoscopy showed submucosal congestion and damage of the entire gastric mucosa,of which the fundus and body of the stomach were most seriously affected.The mucosa was swollen,with a deep purple color,surface erosion and dark red oozing blood.Pathological examination showed bleeding and necrosis of the gastric mucosa,with residual contours of the gastric glands,consistent with ischemic gastritis.CONCLUSION Ischemic gastritis is a rare disease that may be difficult to diagnose as its symptoms may be similar to those of other gastrointestinal diseases.Diagnosis is usually based on endoscopic and pathological examinations,which show insufficient blood supply to the gastric mucosa leading to mucosal damage and necrosis.
文摘In medical science for envisaging human body’s phenomenal structure a major part has been driven by image processing techniques.Major objective of this work is to detect of cerebral atherosclerosis for image segmentation applica-tion.Detection of some abnormal structures in human body has become a difficult task to complete with some simple images.For expounding and distinguishing neural architecture of human brain in an effective manner,MRI(Magnetic Reso-nance Imaging)is one of the most suitable and significant technique.Here we work on detection of Cerebral Atherosclerosis from MRI images of patients.Cer-ebral Atherosclerosis is a cerebral vascular disease causes narrowing of the arteries due to buildup of fatty plaque inside the blood vessels of the brain.It leads to Ischemic stroke if not diagnosed early.Stroke affects majorly old age people and percentage of affected women is more compared to men.Results:Preproces-sing is done by using alpha trimmed meanfilter which is used to remove noise and also it enhances the image.Segmentation of cerebral atherosclerosis is done by using K-means clustering,Contextual clustering,and proposed Hybrid algo-rithm.Various parameters like Correlation,Pixel density,energy is determined and from the analysis of parameters it is determined that proposed Hybrid algo-rithm is efficient.
文摘Background and Purpose: Thrombotic disease is a leading cause of death in industrialized countries. The development of atherosclerosis is a major underlying pathogenesis. Atherosclerotic lesions are largely related to abnormalities in lipid metabolism, and improvement of dietary habits is of great significance. Chlorella is a unicellular organism belonging to the green algae family, and is consumed worldwide as a functional food for the purpose of health promotion due to its excellent nutritional balance including high quality protein. In this study, we investigated the effects of long-term consumption of Chlorella as a food on the development of atherosclerosis and its ability to dissolve thrombi caused by the disruption of the atherosclerotic layer as a functional study of Chlorella. Methods: ApoE<sup>−/−</sup> and Ldlr<sup>−/−</sup> double-knockout mice were fed a chlorella-supplemented experimental diet for 14 weeks. The Entire aorta method was used to measure atherosclerosis development, and the area of sclerotic vessels was evaluated as a percentage of the total area of vessels. In addition, mRNA levels of lipid metabolism-related proteins in the liver and blood vessels were analyzed, as well as blood lipoprotein analysis. Spontaneous thrombolytic activity was measured by measuring the change in volume over time of thrombus formed in microvessel running over the cremaster muscle of the mice using the He-Ne laser-induced thrombus model. Results: There was no significant difference between the two groups in atherosclerosis development compared to the placebo group. However, a significant decrease in SREBP-1 mRNA level and a significant increase in mRNA levels of LXR and CPY71a were observed in the chlorella group. Cholesterol and TG levels in each lipoprotein fraction did not differ between the two groups. On the other hand, thrombolysis in vivo was not significantly different between the two groups in terms of thrombus volume at 60 minutes after thrombus formation. However, a trend toward decreased PAI-1 and TAFI mRNA expression levels was observed in the chlorella group. Conclusion: Intake of chlorella as a food suggested an effect on cholesterol catabolism, increased bile acid synthesis, improved lipid metabolism, and inhibited the development of atherosclerosis. Furthermore, it was suggested that chlorella may suppress the expression of fibrinolytic inhibitory factor and enhance thrombolytic activity.
文摘Objective: To investigate the correlation between fundus atherosclerosis and carotid arterial atherosclerosis. Methods: A total of 516 people undergoing physical examination in Deyang People’s Hospital between June 2020 and December 2022 were randomly selected. Fundus atherosclerosis and carotid arterial atherosclerosis were evaluated by fundus photography and carotid artery ultrasonography, respectively. Results: Among the 516 physical examination patients, 198 (38.4%) had normal fundus examination, and 318 (61.6%) had fundus arteriosclerosis. Among them, 166 cases were of grade I (32.2%), 86 cases were of grade II (16.7%), and 66 cases were of grade III (12.8%). There were 286 cases (55.4%) without carotid atherosclerosis, 201 cases (38.9%) with carotid atherosclerotic plaque, and 33 cases (6.4%) with carotid stenosis. Fundus arteriosclerosis is independently associated with carotid artery intima-media thickness, vulnerable plaques, plaque scores, and carotid artery stenosis (P Conclusion: In summary, there is a close relationship between carotid artery disease and the degree of arteriosclerosis in the eyeground. Fundus photography is a simple, non-invasive, and easily acceptable method of inspection. The results obtained from it are useful in determining the severity of carotid atherosclerosis and guiding early detection and intervention in clinical cases. This can help reduce the incidence of cardiovascular and cerebrovascular diseases.
文摘Calpains are calcium-activated cysteine proteases. There are two main isoforms of calpain that are ubiquitously expressed in tissues, calpain μ or calpain 1, which requires micromolar Ca<sup>2+</sup> for activation, and calpain or 2, which requires millimolar Ca<sup>2+</sup> for activation. The presence of other calpains is tissue specific. Atherosclerosis (AS) is an important risk factor for cerebral infarction, coronary heart disease and peripheral vascular disease. It was originally thought that AS was caused by impaired lipid metabolism. This research briefly reviewed Calpain Family, the structure and activation mechanism of calpain1, Calpains in the pathogenesis of atherosclerosis, NLRP3 structural characteristics and activation, ROS/NLRP3 inflammasome activation mechanism and ROS/NLRP3 inflammasome in atherosclerosis. The research showed that the Calpain-1 may play an important role in mitochondrial ROS/NLRP3 inflammasome in atherosclerosis.
基金supported by a grant from Key Project of Education Commission of Hubei Province(D20202802).
文摘Background:Naodesheng tablets(NDST)was widely used in clinical treatment as a drug for cardiovascular diseases,but the mechanism for treating atherosclerosis was unknown.On the basis of network pharmacology and bioinformatics,predict the relevant targets and signalling pathways for NDST in the treatment of atherosclerosis.Methods:First,the targets of NDST and the targets for treating atherosclerosis were looked for in different databases.Next,Venny 2.1.0 was used to find the genes that overlapped between NDST and targets for treating atherosclerosis.Subsequently,the herb-active ingredient-target-disease were obtained to explore the hub compound.Furthermore,the Metascape database was used for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis.And we constructed the“active ingredient-intersection target-pathway”network by Cytoscape software to gain the hub genes and pathways.Finally,molecular docking was used to verify the affinity of hub ingredients and hub genes.Results:In the results,67 active ingredients and 322 targets of NDST were selected in ingredients-targets network.154 overlapping targets of NDST(322)and atherosclerosis(1330)were obtained.Then,the herb-active ingredient-target-disease showed that quercetin,apigenin and luteolin were the hub ingredients to treat atherosclerosis.Further,the hub genes(PTGS2,RXRA,CASP3)and pathways(lipid and atherosclerosis)were accessed in active ingredient-intersection target-pathway.Finally,the results indicated that quercetin,apigenin and luteolin were better binding the PTGS2,RXRA,CASP3,especially PTGS2 and luteolin in molecular docking.Conclusion:In conclusion,quercetin,apigenin and luteolin,as the main ingredients of NDST could play a important role in PTGS2,RXRA,and CASP3 for treating atherosclerosis via the lipid and atherosclerosis(TNF signaling pathway).
基金Guangxi Key Research and Development Plan Project(Gui Ke AB18221095)China National Region Undergraduate Innovation and Entrepreneurship Training Program Funded Project(No.202110599016)Guangxi Zhuang Autonomous Region Undergraduate Innovation and Entrepreneurship Training Program Funded Project(No.S202210599105).
文摘The objective of this study was to investigate the main active ingredients,potential targets,and possible mechanisms of action of the combination of Radix Astragali and Caulis Spatholobi for the treatment of atherosclerosis using network pharmacology.The study aimed to provide a reference basis for the development of new formulations and clinical use of Chinese medicine.The main components of Radix Astragali and Caulis Spatholobi were obtained from the TCMSP,BATMAN-TCM database,and literature reports.The targets corresponding to the main components were imported into the Uniprot database to standardize the names,and target information was supplemented with the Swiss Target Prediction database.Disease-related targets were obtained from DrugBank,OMIM,CTD,GeneCards,and DisGeNET online databases.Venn tools were used to obtain the potential targets of Radix Astragali and Caulis Spatholobi for the treatment of AS.The intersecting genes were imported into the STRING 11.5 database to construct protein-protein interaction network maps and analyze their interactions.Cytoscape 3.7.1 software was used to mine their core targets.GO function and KEGG signaling pathway enrichment analysis were performed using the DAVID v2023q1 database.The results were imported into the“Bioinformatics Cloud Platform”to generate enrichment bubble maps.Finally,the“component-target-pathway”diagram was constructed using Cytoscape 3.7.1 software.The study found that 78 major active ingredients and 527 potential targets were obtained from Radix Astragali and Caulis Spatholobi.The main active components of the two in combination for the treatment of AS are quercetin,stigmasterol,kaempferol,luteolin,formononetin,etc.The key targets involve CDKN1A,E2F1,CDK4,CDK2,CDK1,RB1,TP53,CDKN1B,IL6,JUN,etc.The main pathways involved the AGE-RAGE signaling pathway in diabetic complications,cancer pathway,etc.The biological processes involved include positive regulation of gene expression,negative regulation of apoptotic process,etc.The study initially verified the feasibility of the combination of Radix Astragali-Caulis Spatholobi by Qi-invigorating(promoting human metabolic activity)and blood-activating for the treatment of AS.It demonstrated that the combination of Chinese medicine has multi-level,multi-target,and multi-pathway mechanisms of action to treat the disease,providing a reference basis for the development and utilization of new drugs.
基金supported by the Educational Commission of Hubei Province of China(D20222802).
文摘Background:The present study intented to delve into the molecular mechanism of Cordyceps sinensis(C.sinensis)in treating atherosclerosis by combining network pharmacology and molecular docking analysis.Methods:We searched the databases including Traditional Chinese Medicines Systems Pharmacology Database and Analysis Platform,PubChem,and PharmMapper to screen out the active chemical ingredients of C.sinensis and the corresponding targets.The String database was used for the matching normalization of results,and the software Cytoscape 3.7.2 was adopted to establish the C.sinensis-active components-targets of action-disease network.The databases of Online Mendelian Inheritance in Man database,GeneCards,Therapeutic Target Database,and DisGNET were searched to yield the major targets of atherosclerosis(AS),which were matched with the active component targets of C.sinensis to identify the potential therapeutic targets.The String database was utilized to set up the protein-protein interaction network,and Cytoscape software was applied for topological analysis,which was followed by the Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes signaling pathway analysis based on the DAVID database.Finally,the core components of C.sinensis and the targets of action were confirmed via molecular docking on AutoDock Vina and PyMOL.Results:In total,7 bioactive ingredients of C.sinensis were identified from Traditional Chinese Medicines Systems Pharmacology Database and Analysis Platform database and 319 predicted targets were obtained,231 of which were associated with AS.The core targets involved in AS treatment with C.sinensis included MAPK1,SRC,PIK3R1,AKT1,and HSP90AA1.The enrichment analysis unveiled the primary pathways involved in these processes,such as pathways in cancer and lipid and atherosclerosis.Moreover,through molecular docking,it was found that the active ingredients of C.sinensis presented with strong binding capacities with their corresponding targets,and the strongest binding capacity was observed between peroxyergosterol and SRC.Conclusions:The present study revealed at the molecular level that C.sinensis played its role in AS treatment through multiple drug active components,targets of action and pathways,which would point out the direction and provide theoretic basis for future research.
文摘Though a century old hypothesis, infection as a cause for atherosclerosis is still a debatable issue. Epidemiological and clinical studies had shown a possible association but inhomogeneity in the study population and study methods along with potential confounders have yielded conflicting results. Infection triggers a chronic inflammatory state which along with other mechanisms such as dyslipidemia, hyper-homocysteinemia, hypercoagulability, impaired glucose metabolism and endothelial dysfunction, contribute in pathogenesis of atherosclerosis. Studies have shown a positive relations between Cytotoxic associated gene-A positive strains of Helicobacter pylori and vascular diseases such as coronary artery disease and stroke. Infection mediated genetic modulation is a new emerging theory in this regard. Further large scale studies on infection and atherosclerosis focusing on multiple pathogenetic mechanisms may help in refining our knowledge in this aspect.
文摘Atherosclerosis is a chronic inflammatory disease associated with cardiovascular dysfunction including myocardial infarction, unstable angina, sudden cardiac death, stroke and peripheral thromboses. It has been predicted that atherosclerosis will be the primary cause of death in the world by 2020. Atherogenesis is initiated by endothelial injury due to oxidative stress associated with cardiovascular risk factors including diabetes mellitus, hypertension, cigarette smoking, dyslipidemia, obesity, and metabolic syndrome. The impairment of the endothelium associated with cardiovascular risk factors creates an imbalance between vasodilating and vasoconstricting factors, in particular, an increase in angiotensin Ⅱ(Ang Ⅱ) and a decrease in nitric oxide. The renin-angiotensin system(RAS), and its primary mediator Ang Ⅱ, also have a direct influence on the progression of the atherosclerotic process via effects on endothelial function, inflammation, fibrinolytic balance, and plaque stability. Anti-inflammatory agents [statins, secretory phospholipase A2 inhibitor, lipoprotein-associated phospholipase A2 inhibitor, 5-lipoxygenase activating protein, chemokine motif ligand-2, C-C chemokine motif receptor 2 pathway inhibitors, methotrexate, IL-1 pathway inhibitor and RAS inhibitors(angiotensin-converting enzyme inhibitors)], Ang Ⅱ receptor blockers and ranin inhibitors may slow inflammatory processes and disease progression. Several studies in human using anti-inflammatory agents and RAS inhibitors revealed vascular benefits and reduced progression of coronary atherosclerosis in patients with stable angina pectoris; decreased vascular inflammatory markers, improved common carotid intima-media thickness and plaque volume in patients with diagnosed atherosclerosis. Recent preclinical studies have demonstrated therapeutic efficacy of vitamin D analogs paricalcitol in Apo E-deficient atherosclerotic mice.
文摘Non-alcoholic fatty liver disease(NAFLD) represents the most common and emerging chronic liver disease worldwide. It includes a wide spectrum of liver diseasesranging from simple fatty liver to non-alcoholic steatohepatitis(NASH),which may progress to fibrosis and more severe liver complications such as cirrhosis,hepatocellular carcinoma and liver mortality. NAFLD is strongly associated with obesity,insulin resistance,hypertension,and dyslipidaemia,and is now regarded as the liver manifestation of the metabolic syndrome. The increased mortality of patients with NAFLD is primarily a result of cardiovascular disease and,to a lesser extent,to liver related diseases. Increased oxidative stress has been reported in both patients with NAFLD and patient with cardiovascular risk factors. Thus,oxidative stress represents a shared pathophysiological disorder between the two conditions. Several therapeutic strategies targeting oxidative stress reduction in patients with NAFLD have been proposed,with conflicting results. In particular,vitamin E supplementation has been suggested for the treatment of non-diabetic,non-cirrhotic adults with active NASH,although this recommendation is based only on the results of a single randomized controlled trial. Other antioxidant treatments suggested are resveratrol,silybin,L-carnitine and pentoxiphylline. No trial so far,has evaluated the cardiovascular effects of antioxidant treatment in patients with NAFLD. New,large-scale studies including as end-point also the assessment of the atherosclerosis markers are needed.
基金Supported by Grants to R.Sessa from Center for Social Disease Research,"Sapienza"University,Rome
文摘Atherosclerotic cardiovascular diseases, chronic inflam-matory diseases of multifactorial etiology, are the lead-ing cause of death worldwide. In the last decade, more infectious agents, labeled as "infectious burden", rather than any single pathogen, have been showed to con-tribute to the development of atherosclerosis through different mechanisms. Some microorganisms, such as Chlamydia pneumoniae(C. pneumoniae), human cytomegalovirus, etc. may act directly on the arterial wall contributing to endothelial dysfunction, foam cell formation, smooth muscle cell proliferation, platelet ag-gregation as well as cytokine, reactive oxygen specie, growth factor, and cellular adhesion molecule produc-tion. Others, such as Helicobacter pylori(H. pylori), in-fluenza virus, etc. may induce a systemic inflammation which in turn may damage the vascular wall(e.g., by cytokines and proteases). Moreover, another indirect mechanism by which some infectious agents(such as H. pylori, C. pneumoniae, periodontal pathogens, etc.) may play a role in the pathogenesis of atherosclero-sis is molecular mimicry. Given the complexity of the mechanisms by which each microorganism may con-tribute to atherosclerosis, defining the interplay of moreinfectious agents is far more difficult because the pro-atherogenic effect of each pathogen might be ampli-fied. Clearly, continued research and a greater aware-ness will be helpful to improve our knowledge on the complex interaction between the infectious burden and atherosclerosis.
基金supported by Natural Sciences and Engineering Research Council of Canada
文摘In this mini-review several commonly used animal models of atherosclerosis have been discussed.Among them,emphasis has been made on mice,rabbits,pigs and non-human primates.Although these animal models have played a significant role in our understanding of induction of atherosclerotic lesions,we still lack a reliable animal model for regression of the disease.Researchers have reported several genetically modified and transgenic animal models that replicate human atherosclerosis,however each of current animal models have some limitations.Among these animal models,the apolipoprotein(apo) E-knockout(KO)mice have been used extensively because they develop spontaneous atherosclerosis.Furthermore,atherosclerotic lesions developed in this model depending on experimental design may resemble humans' stable and unstable atherosclerotic lesions.This mouse model of hypercholesterolemia and atherosclerosis has been also used to investigate the impact of oxidative stress and inflammation on atherogenesis.Low density lipoprotein(LDL)-r-KO mice are a model of human familial hypercholesterolemia.However,unlike apo E-KO mice,the LDL-r-KO mice do not develop spontaneous atherosclerosis.Both apo E-KO and LDL-r-KO mice have been employed to generate other relevant mouse models of cardiovascular disease through breeding strategies.In addition to mice,rabbits have been used extensively particularly to understand the mechanisms of cholesterol-induced atherosclerosis.The present review paper details the characteristics of animal models that are used in atherosclerosis research.
文摘Despite all the therapeutic advances in the field of cardiology, cardiovascular diseases, and in particular coronary artery disease, remain the leading cause of death and disability worldwide, thereby underlining the importance of acquiring new therapeutic options in this field. A reduction in elevated resting heart rate (HR) has long been postulated as a therapeutic approach in the management of cardiovascular disease. An increased HR has been shown to be associated with increased progression of coronary atherosclerosis in animal models and patients. A high HR has also been associated with a greatly increased risk of plaque rupture in patients with coronary atherosclerosis. Endothelial function may be an important link between HR and atherosclerosis. An increased HR has been shown experimentally to cause endothelial dysfunction. Inflammation plays a significant role in the pathogenesis and progression of atherosclerosis. In the literature, there is data that shows an association between HR and circulating markers of vascular inflammation. In addition, HR reduction by pharmacological intervention with ivabradine (a selective HR-lowering agent that acts by inhibiting the pacemaker ionic current If in sinoatrial node cells) reduces the formation of atherosclerotic plaques in animal models of lipid-induced atherosclerosis. The aim of this editorial is to review the possible role of ivabradine on atherosclerosis.
基金Supported by The National Science Council,Taiwan,China,and Changhua Christian Hospital
文摘Mitochondrial physiology and biogenesis play a crucial role in the initiation and progression of cardiovascular disease following oxidative stress-induced damage such as atherosclerosis(AST).Dysfunctional mitochondria caused by an increase in mitochondrial reactive oxygen species(ROS)production,accumulation of mitochondrial DNA damage,and respiratory chain deficiency induces death of endothelial/smooth muscle cells and favors plaque formation/rupture via the regulation of mitochondrial biogenesis-related genes such as peroxisome proliferator-activated receptorγcoactivator(PGC-1),although more detailed mechanisms still need further study.Based on the effect of healthy mitochondria produced by mitochondrial biogenesis on decreasing ROS-mediated cell death and the recent finding that the regulation of PGC-1 involves mitochon- drial fusion-related protein(mitofusin),we thus infer the regulatory role of mitochondrial fusion/fission balance in AST pathophysiology.In this review,the first section discusses the possible association between AST-inducing factors and the molecular regulatory mechanisms of mitochondrial biogenesis and dynamics,and explains the role of mitochondria-dependent regulation in cell apoptosis during AST development. Furthermore,nitric oxide has the Janus-faced effect by protecting vascular damage caused by AST while being a reactive nitrogen species(RNS)which act together with ROS to damage cells.Therefore,in the second section we discuss mitochondrial ATP-sensitive K+ channels,which regulate mitochondrial ion transport to maintain mitochondrial physiology,involved in the regulation of ROS/RNS production and their influence on AST/cardiovascular diseases(CVD).Through this review,we can further appreciate the multi-regulatory functions of the mitochondria involved in AST development.The understanding of these related mechanisms will benefit drug development in treating AST/CVD through targeted biofunctions of mitochondria.
文摘Coronary heart disease is the single most common cause of illness and death in the developed world.Coronary atherosclerosis is by far the most frequent cause of ischemic heart disease,and plaque disruption with superimposed thrombosis is the main cause of the acute coronary syndromes of unstable angina,myocardial infarction,and sudden death.Atherosclerosis is the result of a complex interaction between blood elements,disturbed flow,and vessel wall abnormality,involving several pathological processes:inflammation,with increased endothelial permeability,endothelial activation,and monocyte recruitment;growth,with smooth muscle cell proliferation,migration,and matrix synthesis;degeneration,with lipid accumulation;necrosis,possibly related to the cytotoxic effect of oxidized lipid;calcification/ossification,which may represent an active rather than a dystrophic process;and thrombosis,with platelet recruitment and fibrin formation.In this review we discuss these processes and the possible pathological effects of Chlamydia infection and the ensuing phlogosis.
文摘Mounting evidence supports that a newly identified regulatory T cell (Treg),CD4+LAP+ Treg,is associated with oral tolerance induction and following inhibition of atherosclerosis,but little is described about whether nasal tolerance to antigen likewise induces the novel Tregs production and the relevant antiatherosclerotic benefit.We investigated the effect of nasal administration of heat shock protein-60 (HSP60) on atherogenesis.HSP60 or phosphate buffer solution (PBS) was nasally adminis-tered to six-week-old male ApoE-/-mice.At the 10th week after the nasal administration,there was a significant decrease in atherosclerotic plaque areas of aortic roots in the HSP60-treated mice as com-pared with those in the PBS-treated mice.Atherosclerosis suppression was accompanied with a signifi-cant increase in CD4+LAP+ and CD4+CD25+Foxp3+ Tregs and a concurrently increased production of TGF-β in the HSP60-treated mice.The protective effect of HSP60 was offset by injection of anti-TGF-βantibody.It is concluded that nasal administration of HSP60 can inhibit atherosclerotic formation through immune tolerance which is established by Tregs depending on the induction of anti-inflammatory cytokine TGF-β.Immune tolerance induced by nasal administration of HSP60 may provide an alternative therapeutic method for atherosclerosis.
文摘Hepatitis C virus(HCV)infection represents a major health issue worldwide due to its burden of chronic liver disease and extrahepatic manifestations including cardiovascular diseases,which are associated with excess mortality.Analysis of published studies supports the view that HCV infection should be considered a risk factor for the development of carotid atherosclerosis,heart failure and stroke.In contrast,findings from studies addressing coronary artery disease and HCV have yielded conflicting results.Therefore,meta-analytic reviews and prospective studies are warranted.The pathogenic mechanisms connecting HCV infection,chronic liver disease,and atherogenesis are not completely understood.However,it has been hypothesized that HCV may promote atherogenesis and its complications through several direct and indirect biological mechanisms involving HCV colonization and replication within arterial walls,liver steatosis and fibrosis,enhanced and imbalanced secretion of inflammatory cytokines,oxidative stress,endotoxemia,mixed cryoglobulinemia,perturbed cellular and humoral immunity,hyperhomocysteinemia,hypo-adiponectinaemia,insulin resistance,type 2 diabetes and other components of the metabolic syndrome.Understanding these complex mechanisms is of fundamental importance for the development of novel therapeutic approaches to prevent and to treat vascular complications in patients with chronic HCV infection.Currently,it seems that HCV clearance by interferon and ribavirin treatment significantly reduces non-liver-related mortality;moreover,interferon-based treatment appears to decrease the risk of ischemic stroke.
