Biological nanotechnologies have provided considerable opportunities in the management of malignancies with delicate design and negligible toxicity,from preventive and diagnostic to therapeutic fields.Lipoproteins,bec...Biological nanotechnologies have provided considerable opportunities in the management of malignancies with delicate design and negligible toxicity,from preventive and diagnostic to therapeutic fields.Lipoproteins,because of their inherent blood-brain barrier permeability and lesion-homing capability,have been identified as promising strategies for high-performance theranostics of brain diseases.However,the application of natural lipoproteins remains limited owing to insufficient accumulation and complex purification processes,which can be critical for individual therapeutics and clinical translation.To address these issues,lipoprotein-inspired nano drug-delivery systems(nano-DDSs),which have been learned from nature,have been fabricated to achieve synergistic drug delivery involving site-specific accumulation and tractable preparation with versatile physicochemical functions.In this review,the barriers in brain disease treatment,advantages of state-of-the-art lipoprotein-inspired nano-DDSs,and bio-interactions of such nano-DDSs are highlighted.Furthermore,the characteristics and advanced applications of natural lipoproteins and tailor-made lipoprotein-inspired nano-DDSs are summarized.Specifically,the key designs and current applications of lipoprotein-inspired nano-DDSs in the field of brain disease therapy are intensively discussed.Finally,the current challenges and future perspectives in the field of lipoprotein-inspired nano-DDSs combined with other vehicles,such as exosomes,cell membranes,and bacteria,are discussed.展开更多
Diabetic dyslipidemia is characterized by quantitative and qualitative abnormalities in lipoproteins.In addition to glycation and oxidation,carbamylation is also a post-translational modification affecting lipoprotein...Diabetic dyslipidemia is characterized by quantitative and qualitative abnormalities in lipoproteins.In addition to glycation and oxidation,carbamylation is also a post-translational modification affecting lipoproteins in diabetes.Patients with type 2 diabetes(T2D)exhibit higher levels of carbamylated low-density lipoproteins(cLDL)and high-density lipoproteins(cHDL).Accumulating evidence suggests that cLDL plays a role in atherosclerosis in diabetes.cLDL levels have been shown to predict cardiovascular events and all-cause mortality.cLDL facilitates immune cell recruitment in the vascular wall,promotes accumulation of lipids in macrophages,and contributes to endothelial dysf-unction,endothelial nitric oxide-synthase(eNOS)inactivation and endothelial repair defects.Lastly,cLDL induces thrombus formation and platelet aggregation.On the other hand,recent data have demonstrated that cHDL serum level is independently associated with all-cause and cardiovascular-related mortality in T2D patients.This relationship may be causative since the atheroprotective properties of HDL are altered after carbamylation.Thus,cHDL loses the ability to remove cholesterol from macrophages,to inhibit monocyte adhesion and recruitment,to induce eNOS activation and to inhibit apoptosis.Taken together,it seems very likely that the abnormalities in the biological functions of LDL and HDL after carbamylation contribute to atherosclerosis and to the elevated cardiovascular risk in diabetes.展开更多
Hepatitis C virus(HCV) infects over 150 million people worldwide. In most cases, HCV infection becomes chronic causing liver disease ranging from fibrosis to cirrhosis and hepatocellular carcinoma. Viral persistence a...Hepatitis C virus(HCV) infects over 150 million people worldwide. In most cases, HCV infection becomes chronic causing liver disease ranging from fibrosis to cirrhosis and hepatocellular carcinoma. Viral persistence and pathogenesis are due to the ability of HCV to deregulate specific host processes, mainly lipid metabolism and innate immunity. In particular, HCV exploits the lipoprotein machineries for almost all steps of its life cycle. The aim of this review is to summarize current knowledge concerning the interplay between HCV and lipoprotein metabolism. We discuss the role played by members of lipoproteins in HCV entry, replication and virion production.展开更多
Patients with type 2 diabetes mellitus(T2DM) frequently exhibit macrovascular complications of atherosclerotic cardiovascular(CV) disease. High density lipoproteins(HDL) are protective against atherosclerosis. Low lev...Patients with type 2 diabetes mellitus(T2DM) frequently exhibit macrovascular complications of atherosclerotic cardiovascular(CV) disease. High density lipoproteins(HDL) are protective against atherosclerosis. Low levels of HDL cholesterol(HDL-C) independently contribute to CV risk. Patients with T2 DM not only exhibit low HDL-C, but also dysfunctional HDL. Furthermore, low concentration of HDL may increase the risk for the development of T2 DM through a decreased β cell survival and secretory function. In this paper, we discuss emerging concepts in the relationship of T2 DM with HDL.展开更多
1 INTRODUCTION It’s evident that high level of cholesterol in blood is associated with the formation and devel-opment of familial hypercholestrolemia(FH)and atherosclerosis(AS).In general,choles-terol in blood is mai...1 INTRODUCTION It’s evident that high level of cholesterol in blood is associated with the formation and devel-opment of familial hypercholestrolemia(FH)and atherosclerosis(AS).In general,choles-terol in blood is mainly combined with low-density lipoproteins(LDL),very low-densitylipoproteins(VLDL)and high density lipoproteins(HDL).About 60%-80% cholesterolexists in LDL and VLDL.LDL and VLDL have been recognized as the principal展开更多
AIM:To evaluate the direct binding of two main chlamydial biovars(C.trachomatis and C.pneumoniae) to plasma lipoproteins and its effect on chlamydial infection rate in human hepatoma cell line(HepG2 cells). METHODS:Mu...AIM:To evaluate the direct binding of two main chlamydial biovars(C.trachomatis and C.pneumoniae) to plasma lipoproteins and its effect on chlamydial infection rate in human hepatoma cell line(HepG2 cells). METHODS:Murine plasma lipoproteins were fractionated and isolated using fast-performance liquid chromatography(FPLC),spotted on nitrocellulose membrane and incubated with chlamydial suspensions. Direct binding of chlamydial particles to lipoprotein fractions has been studied using lipopolysaccharide-specific antibodies in immuno-dot blot binding assay and immunoprecipitation analysis.Immunostaining protocol as well as flow cytometry analysis have been employed to study the infectivity rate of chlamydial species in HepG2 cells. RESULTS:Elementary bodies of both C.trachomatis and C.pneumoniae bind ApoB-containing fractions of plasma lipoproteins.That binding becomes stronger when heat-denatured FPLC fractions are used, suggesting a primary role of apolipoproteins in interaction between chlamydial particle and lipoprotein. Both chlamydial biovars efficiently propagate in human hepatoma cell line-HepG2 cells even in serum free conditions forming late-stage inclusion bodies and releasing extracellular elementary bodies.Preincubation of C.trachomatis and C.pneumoniae with native ApoB-containing lipoproteins enhances the rate of chlamydial infection in HepG2 cells.CONCLUSION:A productive infection caused by C. trachomatis and C.pneumoniae may take place in human-derived hepatocytes revealing hepatic cells as possible target in chlamydial infection.Obtained results may suggest the participation of lipoprotein receptors in the mechanism of attachment and/or entry of chlamydial particles into target cells.展开更多
Background. The effects of physical exercises combined with a low-calorie diet on weight loss, body composition, lipoproteins profile, and physical fitness had been well described. However, Central Africa’s studies i...Background. The effects of physical exercises combined with a low-calorie diet on weight loss, body composition, lipoproteins profile, and physical fitness had been well described. However, Central Africa’s studies investigating these kinds of diets and exercise regimens are lacking. Objective. To investigate the effects of adding 14-weeks exercises to a hypocaloric diet on changes in body composition, lipoproteins concentrations, and physical capacities in obese Congolese women. Population and Methods. In total, 34 obese women aged 30 - 39 years (mean age: 33.7 ± 2.4 years) assigned to 14-weeks training program and low energy ketogenic diet. Body composition was assessed using classic methods and impedancemetry. Fasting plasma glucose (FPG) and fasting serum insulin were assessing using enzymatic colorimetric and radioim-munoradiometric methods. HOMA-IR and lipoproteins concentrations were assessed using standardized laboratory methods. VO2peak was measured on a treadmill during a progressive exercise test. Speed, cadence and stride length were measured along the 10-m level walkway. Muscular endurance was measured using the tests of sit-up and inflections-extensions of elbows. All the variables of the study were assessed at the beginning, in the 7-weeks, and in the 14-weeks of training methods. Results. Declines in body weight (16%), percent fat (12.1%), fat weight (26.4%), abdominal fat (34.2%), and waist circumference (10.4%) were found. A significant decrease in FPG (13%), fasting serum insulin (60.9%), HOMA-IR (64.7%), total cholesterol (12.2%), LDL-cholesterol (20.3%), triglycerides (92.8%), and VLDL-triglycerides (17.5%) was shown. In contrast, significant increase in HDL-cholesterol (27.13%) was found. The peak oxygen consumption VO2peak relative to body weight improved more in the 14-weeks training program (13.4%). Obese women exhibited higher values in the 14-weeks training program for speed gait (16.5%), cadence (9.1%), and stride length (15.7%) during normal walk and rapid walk. Weight loss combined with a low-calorie diet and 14-weeks training program improved significantly muscular endurance capacities. Conclusion. Exercise added to hypocaloric diet leads to decreases in body composition, to improve in insulin sensitivity, to enhancement of VO2peak and functional fitness. This may be helpful for the treatment of the metabolic complications of abdominal obesity.展开更多
The pleiotropic functions of circulating high density lipoprotein(HDL) on peripheral vascular health are well established. HDL plays a pivotal role in reverse cholesterol transport and is also known to suppress inflam...The pleiotropic functions of circulating high density lipoprotein(HDL) on peripheral vascular health are well established. HDL plays a pivotal role in reverse cholesterol transport and is also known to suppress inflammation,endothelial activation and apoptosis in peripheral vessels. Although not expressed in the central nervous system, HDL has nevertheless emerged as a potential resilience factor for dementia in multiple epidemiological studies. Animal model data specifically support a role for HDL in attenuating the accumulation of P-amyloid within cerebral vessels concomitant with reduced neuroinflammation and improved cognitive performance. As the vascular contributions to dementia are increasingly appreciated, this review seeks to summarize recent literature focused on the vasoprotective properties of HDL that may extend to cerebral vessels, discuss potential roles of HDL in dementia relative to brainderived lipoproteins, identify gaps in current knowledge, and highlight new opportunities for research and discovery.展开更多
Monocyte chemoattractant protein-1(MCP-1), a potent chemoattractant, is thought to play an important role in migration of monocytes into atherosclerotic lesions. The present study was designed to investigate the capac...Monocyte chemoattractant protein-1(MCP-1), a potent chemoattractant, is thought to play an important role in migration of monocytes into atherosclerotic lesions. The present study was designed to investigate the capacity of human peripheral blood monocytes to express MCP-1 and effects of native very low density lipoprotein (VLDL) and oxidized VLDL(OX-VLDL) on the expression. The total RNA was extracted from cultured monocytes, which were exposed to VLDL and OX-VLDL, and the media conditioned by monocytes were collected. MCP-1 mRNA expression was examined by Northern blot analysis. MCP-1 protein in conditioned media was determined by using sandwich ELISA. The results showed that monocytes can express MCP-1 after a 24 h incubation at 37℃，and the expression was markedly increased by a exposure to OX-VLDL, whereas the expression was slightly increased when exposed to VLDL. It suggests that the capacity of monocytes to produce MCP-1 that recruits and activates circulating monocytes may be of considerable importance in atherogenesis, and oxidation of VLDL enhances its potential to promote atherogenesis.展开更多
Twenty hemodialysis (HD) patients and 20 patients on continuous am-bulatory peritoneal dialysis (CAPD) were investigated for lipids, lipoproteins andapolipoproteins abnormalities. HD patients had elevated serum trigly...Twenty hemodialysis (HD) patients and 20 patients on continuous am-bulatory peritoneal dialysis (CAPD) were investigated for lipids, lipoproteins andapolipoproteins abnormalities. HD patients had elevated serum triglyceride, de-creased high-density lipoprotein cholesterol (HDL-C ) and apolipoprotein A-I(Apo A-I ), whi1e CAPD patients had elevated total cho1esterol, triglyceride,low-density lipoprotein cholesterol (LDL-C), Apolipoprotein B (Apo B), Apo B/Apo A-Iratio, and decreased HDL-C, Apo A-I. Because of the molecular sievingeffects of peritoneum, CAPD have a negative effect on these abnormalities. CAPDpatients might be at greater risk of developing coronary artery disease than HD patients who are also at increased riskas compared with normals.展开更多
Using a novel small-angle X-ray scattering (SAXS) method for determination of fractional and subfractional composition of lipoproteins (LPs), a significant elevation of total cholesterol-lipop- roteins (C-LP) and, esp...Using a novel small-angle X-ray scattering (SAXS) method for determination of fractional and subfractional composition of lipoproteins (LPs), a significant elevation of total cholesterol-lipop- roteins (C-LP) and, especially, total triglyceride- lipoproteins (TG-LP), was shown in this work. Among the LP fractions, poloxamer 407 was shown to significantly increase proatherogenic total C-LDL, TG-LDL and, especially, their precursors C-VLDL and TG-VLDL, while only exhibiting a moderate increase in the antiatherogenic C-HDL and TG-HDL fractions. With regard to the VLDL subfractions, significant elevations were observed in both subfractions studied;namely, C-VLDL1-2 and C-VLDL3-5. Similar chang- es were noted in the TG-VLDL1-2 and TG- VLDL3-5 subfractions. The C-IDL and TG-IDL subfractions were increased significantly (?20- to 30- fold), while the C-LDL1-3 subfraction was moderately (?3- to 5-fold) increased at 48 hrs and at day 4. In the moderately elevated (?2- to 4-fold) anti-atherogenic HDL fraction, the C-HDL2 subfraction was increased more significantly (?4- fold) compared to the C-HDL3 subfraction;how- ever, both C-HDL subfractions returned to base- line by day 4. The elevation in the TG-HDL2 subfraction was observed only at 24 hrs. Mouse models of hyperlipidemia and atherosclerosis are useful to evaluate the role of “individual” LPs, as well as their fractions and subfractions, in hyperlipidemia and the genesis of atherosclerosis.展开更多
Low-density lipoprotein receptor-related protein 2(LRP2)is a multifunctional endocytic receptor expressed in epithelial cells.In mammals,it acts as an endocytic receptor that mediates the cellular uptake of cholestero...Low-density lipoprotein receptor-related protein 2(LRP2)is a multifunctional endocytic receptor expressed in epithelial cells.In mammals,it acts as an endocytic receptor that mediates the cellular uptake of cholesterol-containing apolipoproteins to maintain lipid homeostasis.However,little is known about the role of LRP2 in lipid homeostasis in insects.In the present study,we investigated the function of LRP2 in the migratory locust Locusta migratoria(LmLRP2).The mRNA of LmLRP2 is widely distributed in various tissues,including integument,wing pads,foregut,midgut,hindgut,Malpighian tubules and fat body,and the amounts of LmLRP2 transcripts decreased gradually in the early stages and then increased in the late stages before ecdysis during the nymphal developmental stage.Fluorescence immunohistochemistry revealed that the LmLRP2 protein is mainly located in cellular membranes of the midgut and hindgut.Using RNAi to silence LmLRP2 caused molting defects in nymphs(more than 60%),and the neutral lipid was found to accumulate in the midgut and surface of the integument,but not in the fat body,of dsLmLRP2-treated nymphs.The results of a lipidomics analysis showed that the main components of lipids(diglyceride and triglyceride)were significantly increased in the midgut,but decreased in the fat body and hemolymph.Furthermore,the content of total triglyceride was significantly increased in the midgut,but markedly decreased in the fat body and hemolymph in dsLmLRP2-injected nymphs.Our results indicate that LmLRP2 is located in the cellular membranes of midgut cells,and is required for lipid export from the midgut to the hemolymphand fat body in locusts.展开更多
The limited penetration of nanoparticles and their poor accessibility to cancer cell fractions in tumor remain essential challenges for effective anticancer therapy.Herein,we designed a targeting peptide-decorated bio...The limited penetration of nanoparticles and their poor accessibility to cancer cell fractions in tumor remain essential challenges for effective anticancer therapy.Herein,we designed a targeting peptide-decorated biomimetic lipoprotein(termed as BL-RD)to enable their deep penetration and efficient accessibility to cancer cell fractions in a tumor,thereby improving the combinational chemophotodynamic therapy of triple negative breast cancer.BL-RD was composed of phospholipids,apolipoprotein A1 mimetic peptide(PK22),targeting peptide-conjugated cytotoxic mertansine(RM)and photodynamic agents of DiIC18(5)(DiD).The counterpart biomimetic lipoprotein system without RM(termed as BL-D)was fabricated as control.Both BL-D and BL-RD were nanometer-sized particles with a mean diameter of less than 30 nm and could be efficiently internalized by cancer cells.After intravenous injection,they can be specifically accumulated at tumor sites.When comparing to the counterpart BLD,BL-RD displayed superior capability to permeate across the tumor mass,extravasate from tumor vasculature to distant regions and efficiently access the cancer cell fractions in a solid tumor,thus producing noticeable depression of the tumor growth.Taken together,BL-RD can be a promising delivery nanoplatform with prominent tumor-penetrating and cancer cells-accessing capability for effective tumor therapy.展开更多
High-density lipoproteins(HDL) are naturally-occurring nanoparticles that are biocompatible,non-immunogenic and completely biodegradable. These endogenous particles can circulate for an extended period of time and tra...High-density lipoproteins(HDL) are naturally-occurring nanoparticles that are biocompatible,non-immunogenic and completely biodegradable. These endogenous particles can circulate for an extended period of time and transport lipids, proteins and micro RNA from donor cells to recipient cells.Based on their intrinsic targeting properties, HDL are regarded as promising drug delivery systems. In order to produce on a large scale and to avoid blood borne pollution, reconstituted high-density lipoproteins(rHDL) possessing the biological properties of HDL have been developed. This review summarizes the biological properties and biomedical applications of rHDL as drug delivery platforms. It focuses on the emerging approaches that have been developed for the generation of biomimetic nanoparticles rHDL to overcome the biological barriers to drug delivery, aiming to provide an alternative,promising avenue for efficient targeting transport of nanomedicine.展开更多
Although atherosclerosis is a multifactorial process,proteoglycans mediated lipoprotein(LDL)retention at the subendothelial space is a necessary and sufficient event in provoking lesion initiation.Proteoglycans(PGs)ar...Although atherosclerosis is a multifactorial process,proteoglycans mediated lipoprotein(LDL)retention at the subendothelial space is a necessary and sufficient event in provoking lesion initiation.Proteoglycans(PGs)are usually composed of one core protein backbone with one or more glycosaminoglycan chains(GAGs)covalently linked,mainly include perlecan,biglycan,versican,and decorin.The interaction between LDL and proteoglycans is apparently mediated by the basic amino acids in apoB-100,the moiety of LDL,electrostatic interacting with the negatively charged GAGs(sulfate or carbohydrate groups)of proteoglycans or though some bridge molecules like sphingomyelinase(SMase)or lipoprotein lipase(LpL).In the later section,we collate the promising therapeutic approaches that have been proposed up to now,targeting LDL-PGs interaction.It should be concluded that previous studies on interaction between LDL and PGs mainly focused on perlecan,biglycan,decorin,and versican that all located in the extracellular matrix(ECM),future studies should pay more attention to the endothelial surface glycocalyx and its interaction with LDLs,seeking promising therapeutic targets more specifically.展开更多
Objective:Clinical manifestation of the inflammatory process in its relation to biochemical markers(total cysteine[Cys],cysteine-glycine[CysGly],glutathione[GSH],glutamate-cysteine[Glu-Cys],homocysteine[Hcy],the ratio...Objective:Clinical manifestation of the inflammatory process in its relation to biochemical markers(total cysteine[Cys],cysteine-glycine[CysGly],glutathione[GSH],glutamate-cysteine[Glu-Cys],homocysteine[Hcy],the ratio of reduced to oxidized glutathione[GSH/GSSG],the ratio of reduced to oxidized cysteine[CySH/CySS],malondialdehyde-oxidized low-density lipoproteins[MDA-oxLDL])has been studied in patients with coronavirus disease 2019(COVID-19).Material and methods:48 patients with mild to severe COVID-19 and 20 healthy volunteers were included in our research.The participants were divided into 4 experimental groups according to inflammation intensity estimated based on the serum levels of interleukin 6(IL-6).Results:All 4 groups showed the prevalence of male patients and elevated serum levels of IL-6(by 54.6%).There was no comorbidity in patients with mild COVID-19(nasopharyngitis symptoms)and in healthy control subjects.50%of patients with lung damage had accompanying diseases.Alterations of aminoethyl metabolism were detected in COVID-19 patients:as reflected by the decreased levels of Cys,CysGly,and Glu-Cys and the increased levels of GSH as compared to the control group.Conclusion:Elevation of IL-6 over 7.5 pg/mL was associated with decreased GSH/GSSG and CySH/CySS ratios indicating enhanced oxidative stress and was followed by protein oxidation,specifically MDA-oxLDL.展开更多
The current review article discusses several conditions linked to high cholesterol, including their causes, diagnoses, and treatments. Cardiovascular disease is one of the leading causes of death worldwide, and hyperc...The current review article discusses several conditions linked to high cholesterol, including their causes, diagnoses, and treatments. Cardiovascular disease is one of the leading causes of death worldwide, and hypercholesterolemia is a standalone risk factor for the condition. Numerous cardiovascular illnesses (CVDs) and disorders, including myocardial infarction, hypertension, peripheral vascular diseases, and coronary heart diseases, were highlighted in this article. Low density lipoprotein (LDL) is the key factor in the majority of CVDs. It adheres to fatty deposits and forms plaques inside artery lumen, preventing the heart and other body organs from receiving enough blood and oxygen. Cardiomyopathies and dyslipidemias are the most common causes of morbidity and mortality in men and place a considerable health cost on society. Age, hypertension, obesity-induced blood pressure, and a rise in plasma cholesterol are all factors that raise the risk of coronary heart disease (CHD). Calorie intake must be controlled, meal composition must be changed, a natural cycle must be established, and circadian timeliness must be maintained in order to live a healthy life. To lower the risks of metabolic and cardiovascular diseases, try to go vegetarian and always consume traditional plant-based diets and herbal remedies. Exercise yoga and aerobics every day to stay physically healthy, and have your blood pressure, blood sugar, and cholesterol levels checked on a regular basis. Follow your family doctor’s recommendations for managing high cholesterol risks and diagnosing CVD, obtain a lipid profile, take the recommended medications, maintain composure, and adopt a positive outlook for a long and healthy life.展开更多
Objective Foreign studies have reported that coronary artery disease(CAD) patients with high baseline low-density lipoprotein cholesterol(LDL-C) may have a good prognosis, which is called the “cholesterol paradox”. ...Objective Foreign studies have reported that coronary artery disease(CAD) patients with high baseline low-density lipoprotein cholesterol(LDL-C) may have a good prognosis, which is called the “cholesterol paradox”. This study aimed to examine whether the “cholesterol paradox” also exists in the Chinese population.Methods A total of 2,056 patients who underwent the first percutaneous coronary intervention(PCI)between 2014 and 2016 were enrolled in this retrospective cohort study and classified into two groups based on baseline LDL-C = 2.6 mmol/L(100 mg/d L). The outcomes of interest included major adverse cardiovascular events(MACE), all-cause mortality, recurrent nonfatal myocardial infarction, unexpected coronary revascularization, or any nonfatal stroke.Results All-cause mortality occurred in 8 patients(0.7%) from the low-LDL-C group and 12 patients(2.4%) in the high-LDL-C group, with a significant difference between the two groups(adjusted hazard ratio: 4.030, 95% confidence interval: 1.088–14.934;P = 0.037). However, no significant differences existed for the risk of MACE or other secondary endpoints, such as unexpected revascularization, nor any nonfatal stroke in the two groups.Conclusion In this study, a high baseline LDL-C was not associated with a low risk of clinical outcomes in CAD patients undergoing first PCI, which suggested that the “cholesterol paradox” may be inapplicable to Chinese populations.展开更多
Objective There is a large population of patients classified as complex higher-risk and indicated patients(CHIPs)in China with a poor prognosis.The treatment of these patients is complex and challenging,especially whe...Objective There is a large population of patients classified as complex higher-risk and indicated patients(CHIPs)in China with a poor prognosis.The treatment of these patients is complex and challenging,especially when acute cardiac events occur,such as acute coronary syndrome(ACS)or heart failure.Pharmacotherapy and some mechanical circulatory support(MCS)therapeutic devices can provide stable hemodynamic support for CHIPs-percutaneous coronary intervention(PCI).LDL-C is an important pathogenic factor in atherosclerosis,and the target of blood lipid control.Recent studies have revealed that lipoprotein(a)[Lp(a)],which is formed when a covalent bond between apolipoprotein(a)and apolipoprotein B-100 is made,produces an LDL-like particle.This particle is an independent risk factor for the development of atherosclerosis,and is closely correlated to stent thrombosis and restenosis.Furthermore,this requires active intervention.PCSK9 inhibitors have been used in lipid-lowering treatment,and preventing atherosclerosis.The present study explores the efficacy of PCSK9 inhibitors in CHIPs-ACS,and the association between the change in Lp(a)and survival after 2 years of follow-up.Methods The present real-world,prospective control study enrolled 321 CHIPs-ACS who underwent emergency PCI from August 2019 to November 2020,and these patients were followed up for 2 years.These patients were divided into two groups:PCSK9 group(n=161)given the combined PCSK9 inhibitor(140 mg of evolocumab every 2 weeks)and statins-based therapy,and SOC group(n=160)treated with statin-based lipid-lowering therapy alone.Then,the change in lipid index was measured,and the cardiovascular(CV)event recurrence rate was evaluated after one month and 2 years.Afterwards,the contribution of serum lipid parameters,especially the Lp(a)alteration,in patients with earlier initiation of the PCSK9 inhibitor to the CV outcome was analyzed.Results The LDL-C level was significantly reduced in both groups:52.3%in the PCSK9 group and 32.3%(P<0.001)in the SOC group.It is noteworthy that the Lp(a)level decreased by 13.2%in the PCSK9 group,but increased by 30.3%in the SOC group(P<0.001).Furthermore,the number of CV events was not significantly different between the PCSK9 and SOC groups after the 2-year follow-up period.In the PCSK9 group,the Lp(a)reduction was associated with the baseline Lp(a)levels of the patients(r2=−0.315,P<0.001).Moreover,the decrease in Lp(a)contributed to the decline in CV events in patients who received ACS CHIPs-PCI,and the decrease in Lp(a)level was independent of the LDL-C level reduction.Conclusion The early initiation of PCSK9 inhibitors can significantly reduce the LDL-C and Lp(a)levels in ACS CHIPs-PCI.However,further studies are needed to confirm whether PCSK9 inhibitors can reduce the incidence of CV disease in CHIPs.展开更多
Objective Delayed graft function(DGF)and early graft loss of renal grafts are determined by the quality of the kidneys from the deceased donor.As“non-traditional”risk factors,serum biomarkers of donors,such as lipid...Objective Delayed graft function(DGF)and early graft loss of renal grafts are determined by the quality of the kidneys from the deceased donor.As“non-traditional”risk factors,serum biomarkers of donors,such as lipids and electrolytes,have drawn increasing attention due to their effects on the postoperative outcomes of renal grafts.This study aimed to examine the value of these serum biomarkers for prediction of renal graft function.Methods The present study consecutively collected 306 patients who underwent their first single kidney transplantation(KT)from adult deceased donors in our center from January 1,2018 to December 31,2019.The correlation between postoperative outcomes[DGF and abnormal serum creatinine(SCr)after 6 and 12 months]and risk factors of donors,including gender,age,body mass index(BMI),past histories,serum lipid biomarkers[cholesterol,triglyceride,high-density lipoprotein(HDL)and low-density lipoprotein(DL)],and serum electrolytes(calcium and sodium)were analyzed and evaluated.Results(1)Donor age and pre-existing hypertension were significantly correlated with the incidence rate of DGF and high SCr level(≥2 mg/dL)at 6 and 12 months after KT(P<0.05);(2)The donor’s BMI was significantly correlated with the incidence rate of DGF after KT(P<0.05);(3)For serum lipids,merely the low level of serum HDL of the donor was correlated with the reduced incidence rate of high SCr level at 12 months after KT[P<0.05,OR(95%CI):0.425(0.202–0.97)];(4)The serum calcium of the donor was associated with the reduced incidence rate of high SCr level at 6 and 12 months after KT[P<0.05,OR(95%CI):0.184(0.045–0.747)and P<0.05,OR(95%CI):0.114(0.014–0.948),respectively].Conclusion The serum HDL and calcium of the donor may serve as predictive factors for the postoperative outcomes of renal grafts after KT,in addition to the donor’s age,BMI and pre-existing hypertension.展开更多
基金financial support from the National Natural Science Foundation of China(No.82274104,82074024,82374042)the Open Project of Chinese Materia Medica FirstClass Discipline of Nanjing University of Chinese Medicine(No.2020YLXK019)Young Elite Scientists Sponsorship Program by CACM(No.2021-QNRC2-A01)
文摘Biological nanotechnologies have provided considerable opportunities in the management of malignancies with delicate design and negligible toxicity,from preventive and diagnostic to therapeutic fields.Lipoproteins,because of their inherent blood-brain barrier permeability and lesion-homing capability,have been identified as promising strategies for high-performance theranostics of brain diseases.However,the application of natural lipoproteins remains limited owing to insufficient accumulation and complex purification processes,which can be critical for individual therapeutics and clinical translation.To address these issues,lipoprotein-inspired nano drug-delivery systems(nano-DDSs),which have been learned from nature,have been fabricated to achieve synergistic drug delivery involving site-specific accumulation and tractable preparation with versatile physicochemical functions.In this review,the barriers in brain disease treatment,advantages of state-of-the-art lipoprotein-inspired nano-DDSs,and bio-interactions of such nano-DDSs are highlighted.Furthermore,the characteristics and advanced applications of natural lipoproteins and tailor-made lipoprotein-inspired nano-DDSs are summarized.Specifically,the key designs and current applications of lipoprotein-inspired nano-DDSs in the field of brain disease therapy are intensively discussed.Finally,the current challenges and future perspectives in the field of lipoprotein-inspired nano-DDSs combined with other vehicles,such as exosomes,cell membranes,and bacteria,are discussed.
文摘Diabetic dyslipidemia is characterized by quantitative and qualitative abnormalities in lipoproteins.In addition to glycation and oxidation,carbamylation is also a post-translational modification affecting lipoproteins in diabetes.Patients with type 2 diabetes(T2D)exhibit higher levels of carbamylated low-density lipoproteins(cLDL)and high-density lipoproteins(cHDL).Accumulating evidence suggests that cLDL plays a role in atherosclerosis in diabetes.cLDL levels have been shown to predict cardiovascular events and all-cause mortality.cLDL facilitates immune cell recruitment in the vascular wall,promotes accumulation of lipids in macrophages,and contributes to endothelial dysf-unction,endothelial nitric oxide-synthase(eNOS)inactivation and endothelial repair defects.Lastly,cLDL induces thrombus formation and platelet aggregation.On the other hand,recent data have demonstrated that cHDL serum level is independently associated with all-cause and cardiovascular-related mortality in T2D patients.This relationship may be causative since the atheroprotective properties of HDL are altered after carbamylation.Thus,cHDL loses the ability to remove cholesterol from macrophages,to inhibit monocyte adhesion and recruitment,to induce eNOS activation and to inhibit apoptosis.Taken together,it seems very likely that the abnormalities in the biological functions of LDL and HDL after carbamylation contribute to atherosclerosis and to the elevated cardiovascular risk in diabetes.
基金Supported by AIRC(to Tripodi MNo.IG-13529 to Fimia GM)+6 种基金Ministry for Health of Italy(“Ricerca Corrente”to Grassi GTripodi MAlonzi TFimia GM and Ippolito G“Ricerca Finalizzata”to Fimia GM and Ippolito G)Ministry of University and Research of Italy(PRIN to Tripodi MPh D program to Di Caprio G)
文摘Hepatitis C virus(HCV) infects over 150 million people worldwide. In most cases, HCV infection becomes chronic causing liver disease ranging from fibrosis to cirrhosis and hepatocellular carcinoma. Viral persistence and pathogenesis are due to the ability of HCV to deregulate specific host processes, mainly lipid metabolism and innate immunity. In particular, HCV exploits the lipoprotein machineries for almost all steps of its life cycle. The aim of this review is to summarize current knowledge concerning the interplay between HCV and lipoprotein metabolism. We discuss the role played by members of lipoproteins in HCV entry, replication and virion production.
文摘Patients with type 2 diabetes mellitus(T2DM) frequently exhibit macrovascular complications of atherosclerotic cardiovascular(CV) disease. High density lipoproteins(HDL) are protective against atherosclerosis. Low levels of HDL cholesterol(HDL-C) independently contribute to CV risk. Patients with T2 DM not only exhibit low HDL-C, but also dysfunctional HDL. Furthermore, low concentration of HDL may increase the risk for the development of T2 DM through a decreased β cell survival and secretory function. In this paper, we discuss emerging concepts in the relationship of T2 DM with HDL.
文摘1 INTRODUCTION It’s evident that high level of cholesterol in blood is associated with the formation and devel-opment of familial hypercholestrolemia(FH)and atherosclerosis(AS).In general,choles-terol in blood is mainly combined with low-density lipoproteins(LDL),very low-densitylipoproteins(VLDL)and high density lipoproteins(HDL).About 60%-80% cholesterolexists in LDL and VLDL.LDL and VLDL have been recognized as the principal
文摘AIM:To evaluate the direct binding of two main chlamydial biovars(C.trachomatis and C.pneumoniae) to plasma lipoproteins and its effect on chlamydial infection rate in human hepatoma cell line(HepG2 cells). METHODS:Murine plasma lipoproteins were fractionated and isolated using fast-performance liquid chromatography(FPLC),spotted on nitrocellulose membrane and incubated with chlamydial suspensions. Direct binding of chlamydial particles to lipoprotein fractions has been studied using lipopolysaccharide-specific antibodies in immuno-dot blot binding assay and immunoprecipitation analysis.Immunostaining protocol as well as flow cytometry analysis have been employed to study the infectivity rate of chlamydial species in HepG2 cells. RESULTS:Elementary bodies of both C.trachomatis and C.pneumoniae bind ApoB-containing fractions of plasma lipoproteins.That binding becomes stronger when heat-denatured FPLC fractions are used, suggesting a primary role of apolipoproteins in interaction between chlamydial particle and lipoprotein. Both chlamydial biovars efficiently propagate in human hepatoma cell line-HepG2 cells even in serum free conditions forming late-stage inclusion bodies and releasing extracellular elementary bodies.Preincubation of C.trachomatis and C.pneumoniae with native ApoB-containing lipoproteins enhances the rate of chlamydial infection in HepG2 cells.CONCLUSION:A productive infection caused by C. trachomatis and C.pneumoniae may take place in human-derived hepatocytes revealing hepatic cells as possible target in chlamydial infection.Obtained results may suggest the participation of lipoprotein receptors in the mechanism of attachment and/or entry of chlamydial particles into target cells.
文摘Background. The effects of physical exercises combined with a low-calorie diet on weight loss, body composition, lipoproteins profile, and physical fitness had been well described. However, Central Africa’s studies investigating these kinds of diets and exercise regimens are lacking. Objective. To investigate the effects of adding 14-weeks exercises to a hypocaloric diet on changes in body composition, lipoproteins concentrations, and physical capacities in obese Congolese women. Population and Methods. In total, 34 obese women aged 30 - 39 years (mean age: 33.7 ± 2.4 years) assigned to 14-weeks training program and low energy ketogenic diet. Body composition was assessed using classic methods and impedancemetry. Fasting plasma glucose (FPG) and fasting serum insulin were assessing using enzymatic colorimetric and radioim-munoradiometric methods. HOMA-IR and lipoproteins concentrations were assessed using standardized laboratory methods. VO2peak was measured on a treadmill during a progressive exercise test. Speed, cadence and stride length were measured along the 10-m level walkway. Muscular endurance was measured using the tests of sit-up and inflections-extensions of elbows. All the variables of the study were assessed at the beginning, in the 7-weeks, and in the 14-weeks of training methods. Results. Declines in body weight (16%), percent fat (12.1%), fat weight (26.4%), abdominal fat (34.2%), and waist circumference (10.4%) were found. A significant decrease in FPG (13%), fasting serum insulin (60.9%), HOMA-IR (64.7%), total cholesterol (12.2%), LDL-cholesterol (20.3%), triglycerides (92.8%), and VLDL-triglycerides (17.5%) was shown. In contrast, significant increase in HDL-cholesterol (27.13%) was found. The peak oxygen consumption VO2peak relative to body weight improved more in the 14-weeks training program (13.4%). Obese women exhibited higher values in the 14-weeks training program for speed gait (16.5%), cadence (9.1%), and stride length (15.7%) during normal walk and rapid walk. Weight loss combined with a low-calorie diet and 14-weeks training program improved significantly muscular endurance capacities. Conclusion. Exercise added to hypocaloric diet leads to decreases in body composition, to improve in insulin sensitivity, to enhancement of VO2peak and functional fitness. This may be helpful for the treatment of the metabolic complications of abdominal obesity.
文摘The pleiotropic functions of circulating high density lipoprotein(HDL) on peripheral vascular health are well established. HDL plays a pivotal role in reverse cholesterol transport and is also known to suppress inflammation,endothelial activation and apoptosis in peripheral vessels. Although not expressed in the central nervous system, HDL has nevertheless emerged as a potential resilience factor for dementia in multiple epidemiological studies. Animal model data specifically support a role for HDL in attenuating the accumulation of P-amyloid within cerebral vessels concomitant with reduced neuroinflammation and improved cognitive performance. As the vascular contributions to dementia are increasingly appreciated, this review seeks to summarize recent literature focused on the vasoprotective properties of HDL that may extend to cerebral vessels, discuss potential roles of HDL in dementia relative to brainderived lipoproteins, identify gaps in current knowledge, and highlight new opportunities for research and discovery.
文摘Monocyte chemoattractant protein-1(MCP-1), a potent chemoattractant, is thought to play an important role in migration of monocytes into atherosclerotic lesions. The present study was designed to investigate the capacity of human peripheral blood monocytes to express MCP-1 and effects of native very low density lipoprotein (VLDL) and oxidized VLDL(OX-VLDL) on the expression. The total RNA was extracted from cultured monocytes, which were exposed to VLDL and OX-VLDL, and the media conditioned by monocytes were collected. MCP-1 mRNA expression was examined by Northern blot analysis. MCP-1 protein in conditioned media was determined by using sandwich ELISA. The results showed that monocytes can express MCP-1 after a 24 h incubation at 37℃，and the expression was markedly increased by a exposure to OX-VLDL, whereas the expression was slightly increased when exposed to VLDL. It suggests that the capacity of monocytes to produce MCP-1 that recruits and activates circulating monocytes may be of considerable importance in atherogenesis, and oxidation of VLDL enhances its potential to promote atherogenesis.
文摘Twenty hemodialysis (HD) patients and 20 patients on continuous am-bulatory peritoneal dialysis (CAPD) were investigated for lipids, lipoproteins andapolipoproteins abnormalities. HD patients had elevated serum triglyceride, de-creased high-density lipoprotein cholesterol (HDL-C ) and apolipoprotein A-I(Apo A-I ), whi1e CAPD patients had elevated total cho1esterol, triglyceride,low-density lipoprotein cholesterol (LDL-C), Apolipoprotein B (Apo B), Apo B/Apo A-Iratio, and decreased HDL-C, Apo A-I. Because of the molecular sievingeffects of peritoneum, CAPD have a negative effect on these abnormalities. CAPDpatients might be at greater risk of developing coronary artery disease than HD patients who are also at increased riskas compared with normals.
文摘Using a novel small-angle X-ray scattering (SAXS) method for determination of fractional and subfractional composition of lipoproteins (LPs), a significant elevation of total cholesterol-lipop- roteins (C-LP) and, especially, total triglyceride- lipoproteins (TG-LP), was shown in this work. Among the LP fractions, poloxamer 407 was shown to significantly increase proatherogenic total C-LDL, TG-LDL and, especially, their precursors C-VLDL and TG-VLDL, while only exhibiting a moderate increase in the antiatherogenic C-HDL and TG-HDL fractions. With regard to the VLDL subfractions, significant elevations were observed in both subfractions studied;namely, C-VLDL1-2 and C-VLDL3-5. Similar chang- es were noted in the TG-VLDL1-2 and TG- VLDL3-5 subfractions. The C-IDL and TG-IDL subfractions were increased significantly (?20- to 30- fold), while the C-LDL1-3 subfraction was moderately (?3- to 5-fold) increased at 48 hrs and at day 4. In the moderately elevated (?2- to 4-fold) anti-atherogenic HDL fraction, the C-HDL2 subfraction was increased more significantly (?4- fold) compared to the C-HDL3 subfraction;how- ever, both C-HDL subfractions returned to base- line by day 4. The elevation in the TG-HDL2 subfraction was observed only at 24 hrs. Mouse models of hyperlipidemia and atherosclerosis are useful to evaluate the role of “individual” LPs, as well as their fractions and subfractions, in hyperlipidemia and the genesis of atherosclerosis.
基金supported by the National Key R&D Program of China (2022YFE0196200)the National Natural Science Foundation of China–Deutsche Forschungsgemeinschaft of Germany (31761133021)+3 种基金the National Natural Science Foundation of China (31970469 and 31701794)the earmarked fund for Modern Agro-industry Technology Research System, China (2023CYJSTX01-20)the Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi, China (2017104)the Fund for Shanxi “1331 Project”, China
文摘Low-density lipoprotein receptor-related protein 2(LRP2)is a multifunctional endocytic receptor expressed in epithelial cells.In mammals,it acts as an endocytic receptor that mediates the cellular uptake of cholesterol-containing apolipoproteins to maintain lipid homeostasis.However,little is known about the role of LRP2 in lipid homeostasis in insects.In the present study,we investigated the function of LRP2 in the migratory locust Locusta migratoria(LmLRP2).The mRNA of LmLRP2 is widely distributed in various tissues,including integument,wing pads,foregut,midgut,hindgut,Malpighian tubules and fat body,and the amounts of LmLRP2 transcripts decreased gradually in the early stages and then increased in the late stages before ecdysis during the nymphal developmental stage.Fluorescence immunohistochemistry revealed that the LmLRP2 protein is mainly located in cellular membranes of the midgut and hindgut.Using RNAi to silence LmLRP2 caused molting defects in nymphs(more than 60%),and the neutral lipid was found to accumulate in the midgut and surface of the integument,but not in the fat body,of dsLmLRP2-treated nymphs.The results of a lipidomics analysis showed that the main components of lipids(diglyceride and triglyceride)were significantly increased in the midgut,but decreased in the fat body and hemolymph.Furthermore,the content of total triglyceride was significantly increased in the midgut,but markedly decreased in the fat body and hemolymph in dsLmLRP2-injected nymphs.Our results indicate that LmLRP2 is located in the cellular membranes of midgut cells,and is required for lipid export from the midgut to the hemolymphand fat body in locusts.
基金financially supported by the National Basic Research Program of China(2015CB932103)the National Natural Science Foundation of China(31771092,81521005,81690265)the Youth Innovation Promotion Association of Chinese Academy of Sciences and Fudan-SIMM Joint Research Fund(FU-SIMM20182005,China).
文摘The limited penetration of nanoparticles and their poor accessibility to cancer cell fractions in tumor remain essential challenges for effective anticancer therapy.Herein,we designed a targeting peptide-decorated biomimetic lipoprotein(termed as BL-RD)to enable their deep penetration and efficient accessibility to cancer cell fractions in a tumor,thereby improving the combinational chemophotodynamic therapy of triple negative breast cancer.BL-RD was composed of phospholipids,apolipoprotein A1 mimetic peptide(PK22),targeting peptide-conjugated cytotoxic mertansine(RM)and photodynamic agents of DiIC18(5)(DiD).The counterpart biomimetic lipoprotein system without RM(termed as BL-D)was fabricated as control.Both BL-D and BL-RD were nanometer-sized particles with a mean diameter of less than 30 nm and could be efficiently internalized by cancer cells.After intravenous injection,they can be specifically accumulated at tumor sites.When comparing to the counterpart BLD,BL-RD displayed superior capability to permeate across the tumor mass,extravasate from tumor vasculature to distant regions and efficiently access the cancer cell fractions in a solid tumor,thus producing noticeable depression of the tumor growth.Taken together,BL-RD can be a promising delivery nanoplatform with prominent tumor-penetrating and cancer cells-accessing capability for effective tumor therapy.
基金supported by National Natural Science Foundation of China (Nos. 81373351, 81573382, and 81722043)grant from Shanghai Science and Technology Committee (15540723700)"Shu Guang" project supported by Shanghai Municipal Education Commission and Shanghai Education Development Foundation (15SG14)
文摘High-density lipoproteins(HDL) are naturally-occurring nanoparticles that are biocompatible,non-immunogenic and completely biodegradable. These endogenous particles can circulate for an extended period of time and transport lipids, proteins and micro RNA from donor cells to recipient cells.Based on their intrinsic targeting properties, HDL are regarded as promising drug delivery systems. In order to produce on a large scale and to avoid blood borne pollution, reconstituted high-density lipoproteins(rHDL) possessing the biological properties of HDL have been developed. This review summarizes the biological properties and biomedical applications of rHDL as drug delivery platforms. It focuses on the emerging approaches that have been developed for the generation of biomimetic nanoparticles rHDL to overcome the biological barriers to drug delivery, aiming to provide an alternative,promising avenue for efficient targeting transport of nanomedicine.
基金supported by Grants-in-Aid from the National Natural Science Foundation of China(No.31870940,11772036,11572028,11421202)National Key Research and Development Program in China(No.2017YFB0702501)the Fundamental Research Funds for the Central Universities.
文摘Although atherosclerosis is a multifactorial process,proteoglycans mediated lipoprotein(LDL)retention at the subendothelial space is a necessary and sufficient event in provoking lesion initiation.Proteoglycans(PGs)are usually composed of one core protein backbone with one or more glycosaminoglycan chains(GAGs)covalently linked,mainly include perlecan,biglycan,versican,and decorin.The interaction between LDL and proteoglycans is apparently mediated by the basic amino acids in apoB-100,the moiety of LDL,electrostatic interacting with the negatively charged GAGs(sulfate or carbohydrate groups)of proteoglycans or though some bridge molecules like sphingomyelinase(SMase)or lipoprotein lipase(LpL).In the later section,we collate the promising therapeutic approaches that have been proposed up to now,targeting LDL-PGs interaction.It should be concluded that previous studies on interaction between LDL and PGs mainly focused on perlecan,biglycan,decorin,and versican that all located in the extracellular matrix(ECM),future studies should pay more attention to the endothelial surface glycocalyx and its interaction with LDLs,seeking promising therapeutic targets more specifically.
基金This study was approved by the Medical Ethics Commission of Chita State Medical Academy(No.104,2020-11-11)informed consent in writing was provided by the legal guardians.
文摘Objective:Clinical manifestation of the inflammatory process in its relation to biochemical markers(total cysteine[Cys],cysteine-glycine[CysGly],glutathione[GSH],glutamate-cysteine[Glu-Cys],homocysteine[Hcy],the ratio of reduced to oxidized glutathione[GSH/GSSG],the ratio of reduced to oxidized cysteine[CySH/CySS],malondialdehyde-oxidized low-density lipoproteins[MDA-oxLDL])has been studied in patients with coronavirus disease 2019(COVID-19).Material and methods:48 patients with mild to severe COVID-19 and 20 healthy volunteers were included in our research.The participants were divided into 4 experimental groups according to inflammation intensity estimated based on the serum levels of interleukin 6(IL-6).Results:All 4 groups showed the prevalence of male patients and elevated serum levels of IL-6(by 54.6%).There was no comorbidity in patients with mild COVID-19(nasopharyngitis symptoms)and in healthy control subjects.50%of patients with lung damage had accompanying diseases.Alterations of aminoethyl metabolism were detected in COVID-19 patients:as reflected by the decreased levels of Cys,CysGly,and Glu-Cys and the increased levels of GSH as compared to the control group.Conclusion:Elevation of IL-6 over 7.5 pg/mL was associated with decreased GSH/GSSG and CySH/CySS ratios indicating enhanced oxidative stress and was followed by protein oxidation,specifically MDA-oxLDL.
文摘The current review article discusses several conditions linked to high cholesterol, including their causes, diagnoses, and treatments. Cardiovascular disease is one of the leading causes of death worldwide, and hypercholesterolemia is a standalone risk factor for the condition. Numerous cardiovascular illnesses (CVDs) and disorders, including myocardial infarction, hypertension, peripheral vascular diseases, and coronary heart diseases, were highlighted in this article. Low density lipoprotein (LDL) is the key factor in the majority of CVDs. It adheres to fatty deposits and forms plaques inside artery lumen, preventing the heart and other body organs from receiving enough blood and oxygen. Cardiomyopathies and dyslipidemias are the most common causes of morbidity and mortality in men and place a considerable health cost on society. Age, hypertension, obesity-induced blood pressure, and a rise in plasma cholesterol are all factors that raise the risk of coronary heart disease (CHD). Calorie intake must be controlled, meal composition must be changed, a natural cycle must be established, and circadian timeliness must be maintained in order to live a healthy life. To lower the risks of metabolic and cardiovascular diseases, try to go vegetarian and always consume traditional plant-based diets and herbal remedies. Exercise yoga and aerobics every day to stay physically healthy, and have your blood pressure, blood sugar, and cholesterol levels checked on a regular basis. Follow your family doctor’s recommendations for managing high cholesterol risks and diagnosing CVD, obtain a lipid profile, take the recommended medications, maintain composure, and adopt a positive outlook for a long and healthy life.
基金supported by the Ethics Committee of Sir Run Run Shaw Hospital of Zhejiang University [NO.20200224-33]Key Project of Medical and Health Science and Technology of Zhejiang Province [NO. WKJ-ZJ-1715]+7 种基金Zhejiang Province Traditional Chinese Medicine Science and Technology Project [NO. 2017ZA006]Natural Science Foundation of Zhejiang Province [NO. LQ17H020006]Medical health Science and Technology project of Zhejiang Province [NO. 2017KY207]National Natural Science Foundation of China [82070408]Medical and health project [2021RC014]Hangzhou Medical Health Science and Technology Project [B20200116]“Pioneer” and “Leading Goose” R&D Program of Zhejiang[2023C04013]Administration of Traditional Chinese Medicine of Zhejiang Province [GZY-ZJ-KJ-23001]。
文摘Objective Foreign studies have reported that coronary artery disease(CAD) patients with high baseline low-density lipoprotein cholesterol(LDL-C) may have a good prognosis, which is called the “cholesterol paradox”. This study aimed to examine whether the “cholesterol paradox” also exists in the Chinese population.Methods A total of 2,056 patients who underwent the first percutaneous coronary intervention(PCI)between 2014 and 2016 were enrolled in this retrospective cohort study and classified into two groups based on baseline LDL-C = 2.6 mmol/L(100 mg/d L). The outcomes of interest included major adverse cardiovascular events(MACE), all-cause mortality, recurrent nonfatal myocardial infarction, unexpected coronary revascularization, or any nonfatal stroke.Results All-cause mortality occurred in 8 patients(0.7%) from the low-LDL-C group and 12 patients(2.4%) in the high-LDL-C group, with a significant difference between the two groups(adjusted hazard ratio: 4.030, 95% confidence interval: 1.088–14.934;P = 0.037). However, no significant differences existed for the risk of MACE or other secondary endpoints, such as unexpected revascularization, nor any nonfatal stroke in the two groups.Conclusion In this study, a high baseline LDL-C was not associated with a low risk of clinical outcomes in CAD patients undergoing first PCI, which suggested that the “cholesterol paradox” may be inapplicable to Chinese populations.
基金the Translational Medicine and Interdisciplinary Research Joint Fund of Zhongnan Hospital of Wuhan University(No.ZNLH-201907)the Hubei Province Health and Family Planning Scientific Research Project(No.WJ2019Q041)the Chinese Academy of Medical Science Innovation Fund for Medical Sciences(No.2021-I2M-1-009).
文摘Objective There is a large population of patients classified as complex higher-risk and indicated patients(CHIPs)in China with a poor prognosis.The treatment of these patients is complex and challenging,especially when acute cardiac events occur,such as acute coronary syndrome(ACS)or heart failure.Pharmacotherapy and some mechanical circulatory support(MCS)therapeutic devices can provide stable hemodynamic support for CHIPs-percutaneous coronary intervention(PCI).LDL-C is an important pathogenic factor in atherosclerosis,and the target of blood lipid control.Recent studies have revealed that lipoprotein(a)[Lp(a)],which is formed when a covalent bond between apolipoprotein(a)and apolipoprotein B-100 is made,produces an LDL-like particle.This particle is an independent risk factor for the development of atherosclerosis,and is closely correlated to stent thrombosis and restenosis.Furthermore,this requires active intervention.PCSK9 inhibitors have been used in lipid-lowering treatment,and preventing atherosclerosis.The present study explores the efficacy of PCSK9 inhibitors in CHIPs-ACS,and the association between the change in Lp(a)and survival after 2 years of follow-up.Methods The present real-world,prospective control study enrolled 321 CHIPs-ACS who underwent emergency PCI from August 2019 to November 2020,and these patients were followed up for 2 years.These patients were divided into two groups:PCSK9 group(n=161)given the combined PCSK9 inhibitor(140 mg of evolocumab every 2 weeks)and statins-based therapy,and SOC group(n=160)treated with statin-based lipid-lowering therapy alone.Then,the change in lipid index was measured,and the cardiovascular(CV)event recurrence rate was evaluated after one month and 2 years.Afterwards,the contribution of serum lipid parameters,especially the Lp(a)alteration,in patients with earlier initiation of the PCSK9 inhibitor to the CV outcome was analyzed.Results The LDL-C level was significantly reduced in both groups:52.3%in the PCSK9 group and 32.3%(P<0.001)in the SOC group.It is noteworthy that the Lp(a)level decreased by 13.2%in the PCSK9 group,but increased by 30.3%in the SOC group(P<0.001).Furthermore,the number of CV events was not significantly different between the PCSK9 and SOC groups after the 2-year follow-up period.In the PCSK9 group,the Lp(a)reduction was associated with the baseline Lp(a)levels of the patients(r2=−0.315,P<0.001).Moreover,the decrease in Lp(a)contributed to the decline in CV events in patients who received ACS CHIPs-PCI,and the decrease in Lp(a)level was independent of the LDL-C level reduction.Conclusion The early initiation of PCSK9 inhibitors can significantly reduce the LDL-C and Lp(a)levels in ACS CHIPs-PCI.However,further studies are needed to confirm whether PCSK9 inhibitors can reduce the incidence of CV disease in CHIPs.
基金The study was supported by the Innovation Team Fund Project of Hubei Province(No.WJ2021C001)the Key Research and Development Plan of Hubei Province(No.2022BCA015).
文摘Objective Delayed graft function(DGF)and early graft loss of renal grafts are determined by the quality of the kidneys from the deceased donor.As“non-traditional”risk factors,serum biomarkers of donors,such as lipids and electrolytes,have drawn increasing attention due to their effects on the postoperative outcomes of renal grafts.This study aimed to examine the value of these serum biomarkers for prediction of renal graft function.Methods The present study consecutively collected 306 patients who underwent their first single kidney transplantation(KT)from adult deceased donors in our center from January 1,2018 to December 31,2019.The correlation between postoperative outcomes[DGF and abnormal serum creatinine(SCr)after 6 and 12 months]and risk factors of donors,including gender,age,body mass index(BMI),past histories,serum lipid biomarkers[cholesterol,triglyceride,high-density lipoprotein(HDL)and low-density lipoprotein(DL)],and serum electrolytes(calcium and sodium)were analyzed and evaluated.Results(1)Donor age and pre-existing hypertension were significantly correlated with the incidence rate of DGF and high SCr level(≥2 mg/dL)at 6 and 12 months after KT(P<0.05);(2)The donor’s BMI was significantly correlated with the incidence rate of DGF after KT(P<0.05);(3)For serum lipids,merely the low level of serum HDL of the donor was correlated with the reduced incidence rate of high SCr level at 12 months after KT[P<0.05,OR(95%CI):0.425(0.202–0.97)];(4)The serum calcium of the donor was associated with the reduced incidence rate of high SCr level at 6 and 12 months after KT[P<0.05,OR(95%CI):0.184(0.045–0.747)and P<0.05,OR(95%CI):0.114(0.014–0.948),respectively].Conclusion The serum HDL and calcium of the donor may serve as predictive factors for the postoperative outcomes of renal grafts after KT,in addition to the donor’s age,BMI and pre-existing hypertension.
