Aim To investigate the anti-atherosclerotic mechanisms of the novel compoundpivanampeta in the early and later stages of atherosclerosis evolution. Methods Rats or rabbits wererandomly assigned to the control, the mod...Aim To investigate the anti-atherosclerotic mechanisms of the novel compoundpivanampeta in the early and later stages of atherosclerosis evolution. Methods Rats or rabbits wererandomly assigned to the control, the model and the pivanampeta-treated groups. The rats or rabbitsin the model group and the pivanampeta-treated group were fed with hypercholesterol diet. Thecarotids of rabbits were cut into pieces and stained with HE. The rat or rabbit serum levels of TC,LDL-CHO, HDL-CHO, IL-8, ET-1, PGI_2, TXA_2, and NO were assayed. The expressions of MCP-1 and IL-8mRNA on rabbit carotid were determined by semi-quantitative RT-PCR. Results Pivanampeta exerted aninhibitory effect on TXA_2 formation without PGI_2 production in the early and later stages ofatherosclerosis. The significantly increased release of NO and the decreased release of IL-8 in theanimals in pivanampeta-treated group were both detected in the rat atherosclerosis model. In therabbit atherosclerosis model the expressions of IL-8 and MCP-1 mRNA in pivanampeta-treated groupwere decreased significantly. However, the treatment with pivanampeta had no effect on the levels ofplasma cholesterol, MDA and SOD. Conclusion The increase of serum NO contents and the decrease ofplasma TXA_2 level, as well as its inhibition of expression of IL-8 and MCP-1 are probably involvedin the mechanisms underlying the anti-atherosclerotic effects of pivanampeta.展开更多
Objective: To study the cause and mechanism of transplantation vasculopathy which characterized by accelerated graft arteriosclerosis (AGA), we established a mouse aorta graft model. Methods: A segment of thoracic aor...Objective: To study the cause and mechanism of transplantation vasculopathy which characterized by accelerated graft arteriosclerosis (AGA), we established a mouse aorta graft model. Methods: A segment of thoracic aortas of B10.A (2R) mice were transplanted to C57BL/10 mice abdominal aorta by end to side anastomoses. The different time point collected grafts were analyzed by morphological, histochemical and electro microscopic methods. Results: Rejection was manifested as a concentric progressive destruction of the smooth muscle cells. In contrast, the endothelial inflammation and subsequent neointimal proliferation characteristic of AGA was localized to the regions of turbulent flow, i.e. the junction of the graft with the recipient aorta. Conclusion: This model separates the processes of rejection and neointimal formation which usually manifested together in the lesion of AGA, elucidate that different mechanisms control vascular rejection and neointimal formation in chronic rejection.展开更多
The stent was a major breakthrough in the treatment of atherosclerotic vascular disease. The permanent vascular implant of a stent, however, changes the intra-stent blood flow hemodynamics. There is a growing consensu...The stent was a major breakthrough in the treatment of atherosclerotic vascular disease. The permanent vascular implant of a stent, however, changes the intra-stent blood flow hemodynamics. There is a growing consensus that the stent implant may change the artery wall shear stress distribution and hence lead to the restenosis process. Computational fluid dynamics （CFD） has been widely used to analyze hemodynamics in stented arteries. In this paper, two CFD models （the axisymmetric model and the 3-D stent model） were developed to investigate the effects of strut geometry and blood rheology on the intra-stent hemodynamics. The velocity profile, flow recirculation, and wall shear stress distribution of various stent strut geometries were studied. Results show strong correlations between the intra-stent hemodynamics and strut geometry. The intra-stent blood flow is very sensitive to the strut height and fillet size. A round strut with a large fillet size shows 36% and 34% reductions in key parameters evaluating the restenosis risk for the axisymmetric model and the 3-D stent model, respectively. This suggests that electrochemical polishing, a surface-improving process during stent manufacturing, strongly influences the hemodynamic behavior in stented arteries and should be controlled precisely in order to achieve the best clinical outcome. Rheological effects on the wall shear stress are minor in both axisymmetric and 3-D stent models for the vessel diameter of 4 mm, with Newtonian flow simulation tending to give more conservative estimates ofrestenosis risk. Therefore, it is reasonable to simulate the blood flow as a Newtonian flow in stented arteries using the simpler axisymmetric model. These findings will provide great insights for stent design optimization for potential restenosis improvement.展开更多
Objective:Early detection of atherosclerotic renal artery stenosis (ARAS) is clinically important with respect to blood pressure control, prevention of renal insufficiency, and even improving survival. We investigated...Objective:Early detection of atherosclerotic renal artery stenosis (ARAS) is clinically important with respect to blood pressure control, prevention of renal insufficiency, and even improving survival. We investigated whether the presence of significant ARAS (luminal diameter narrowing ≥70%) could be predicted using a logistic regression model before coronary angiography/intervention. Methods:Initially, we developed a logistic regression model for detecting significant ARAS based upon clinical and angiographic features and biochemical measurements in a cohort of 1 813 patients undergoing transfemoral coronary and renal angiography. This model was then prospectively applied to an additional 495 patients who received transradial renal angiography to ascertain its predictive accuracy for the presence of significant ARAS. Results:Multivariate regression analysis revealed that older age (≥65 years), resistant hypertension, type 2 diabetes, creatinine clearance (Ccr) ≤60 ml/min, and multivessel coronary disease were independent predictors for significant ARAS. A logistic regression model for detecting ARAS by incorporating conventional risk factors and multivessel coronary disease was generated as:P/(1 P)=exp( 2.618+1.112[age≥65 years]+1.891[resistant hypertension]+0.453[type 2 diabetes]+0.587[Ccr≤60 ml/min]+2.254[multivessel coronary disease]). When this regression model was prospectively applied to the additional 495 patients undergoing transradial coronary and renal angiography, significant ARAS could be detected with a sensitivity of 81.2%, specificity of 88.9%, and positive and negative predictive accuracies of 53.8% and 96.7%, respectively. Conclusions:The logistic regression model generated in this study may be useful for screening for significant ARAS in patients undergoing transradial coronary angiography/intervention.展开更多
Complement component 5a(C5a)is a 74 amino acid glycoprotein and an important proinflammatory mediator that is cleaved enzymatically from its precursor,C5,on activation of the complement cascade.C5a is quickly metaboli...Complement component 5a(C5a)is a 74 amino acid glycoprotein and an important proinflammatory mediator that is cleaved enzymatically from its precursor,C5,on activation of the complement cascade.C5a is quickly metabolised by carboxypeptidases,forming the less-potent C5a desArg.C5a and C5a desArg interact with their receptors(C5aR and C5L2),which results in a number of effects which are essential to the immune response.C5a has a broad range of biological effects throughout the human body because the widespread expression of C5a receptors throughout the human organs enables C5a and C5a desArg to elicit a broad range of biological effects.Recently,accumulating evidence in humans and experimental animal models shows that the C5a-C5aR axis is involved in the development of atherosclerosis lesions.The absence or blockade of C5aRs greatly reduces the formation of atherosclerotic lesions or wire-injury-induced neointima formation in atherosclerosis-prone mice.Serum C5a level was related to the major adverse cardiovascular events in patients with advanced atherosclerosis and those with drug-eluting stent implantation.Thus,the C5a-C5aR axis may be a significant pathogenic driver of arteriosclerotic vascular disease,making C5a-C5aR inhibition an attractive therapeutic strategy.展开更多
Objective: To observe the preventive role of Suxiao Jiuxin Pill (SX速效救心丸) on atherosclerosis (AS) and to probe into the mechanism in the atherosclerosis rat model. Methods: The AS rat model was established by a h...Objective: To observe the preventive role of Suxiao Jiuxin Pill (SX速效救心丸) on atherosclerosis (AS) and to probe into the mechanism in the atherosclerosis rat model. Methods: The AS rat model was established by a high fat diet and a large dose of calcium (vitamin D3, 0.6 million U/kg, i.p, once). Sixty healthy male adult Sprague-Dawlay (SD) rats were randomly divided into 6 groups, a normal control group (N), a model group (M), a SX low dose group (SXL), a SX middle dose group (SXM), a SX high dose group (SXH), and an atorvastatin group (ATO) (n=10 in each group). The rats in the treatment groups were given with the specific drugs from the first day by oral administration, and the normal control group and the model group were given with normal saline for 12 weeks. Afterwards, the content of malondialdehyde (MDA), the activity of superoxide dismutase (SOD) and the content of oxidized low density lipoprotein (ox-LDL) in the serum were detected. In addition, the expression of peroxisome proliferator-activated receptor γ (PPARγ) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) proteins were tested by Western-blot method. Results: The serum ox-LDL and MDA level significantly decreased, SOD activity increased in the SX middle, high dose groups and the atorvastatin group compared to the model group (all P<0.05). While the expression of PPARγ and NF-κb proteins significantly decreased in the SX low, middle, high dose groups and the atorvastatin group compared to the model group (all P<0.01), with the best effect in the SX high dose group .These results indicate that SX could elevate the activity of serum SOD, decrease serum level of MDA and ox-LDL, and reduce the expression of PPARγ and NF-κB proteins. Conclusion: SX plays an important role in anti-inflammation and inhibition of oxidative stress, which possibly are the mechanism of its preventing and treating atherosclerosis.展开更多
文摘Aim To investigate the anti-atherosclerotic mechanisms of the novel compoundpivanampeta in the early and later stages of atherosclerosis evolution. Methods Rats or rabbits wererandomly assigned to the control, the model and the pivanampeta-treated groups. The rats or rabbitsin the model group and the pivanampeta-treated group were fed with hypercholesterol diet. Thecarotids of rabbits were cut into pieces and stained with HE. The rat or rabbit serum levels of TC,LDL-CHO, HDL-CHO, IL-8, ET-1, PGI_2, TXA_2, and NO were assayed. The expressions of MCP-1 and IL-8mRNA on rabbit carotid were determined by semi-quantitative RT-PCR. Results Pivanampeta exerted aninhibitory effect on TXA_2 formation without PGI_2 production in the early and later stages ofatherosclerosis. The significantly increased release of NO and the decreased release of IL-8 in theanimals in pivanampeta-treated group were both detected in the rat atherosclerosis model. In therabbit atherosclerosis model the expressions of IL-8 and MCP-1 mRNA in pivanampeta-treated groupwere decreased significantly. However, the treatment with pivanampeta had no effect on the levels ofplasma cholesterol, MDA and SOD. Conclusion The increase of serum NO contents and the decrease ofplasma TXA_2 level, as well as its inhibition of expression of IL-8 and MCP-1 are probably involvedin the mechanisms underlying the anti-atherosclerotic effects of pivanampeta.
文摘Objective: To study the cause and mechanism of transplantation vasculopathy which characterized by accelerated graft arteriosclerosis (AGA), we established a mouse aorta graft model. Methods: A segment of thoracic aortas of B10.A (2R) mice were transplanted to C57BL/10 mice abdominal aorta by end to side anastomoses. The different time point collected grafts were analyzed by morphological, histochemical and electro microscopic methods. Results: Rejection was manifested as a concentric progressive destruction of the smooth muscle cells. In contrast, the endothelial inflammation and subsequent neointimal proliferation characteristic of AGA was localized to the regions of turbulent flow, i.e. the junction of the graft with the recipient aorta. Conclusion: This model separates the processes of rejection and neointimal formation which usually manifested together in the lesion of AGA, elucidate that different mechanisms control vascular rejection and neointimal formation in chronic rejection.
文摘The stent was a major breakthrough in the treatment of atherosclerotic vascular disease. The permanent vascular implant of a stent, however, changes the intra-stent blood flow hemodynamics. There is a growing consensus that the stent implant may change the artery wall shear stress distribution and hence lead to the restenosis process. Computational fluid dynamics （CFD） has been widely used to analyze hemodynamics in stented arteries. In this paper, two CFD models （the axisymmetric model and the 3-D stent model） were developed to investigate the effects of strut geometry and blood rheology on the intra-stent hemodynamics. The velocity profile, flow recirculation, and wall shear stress distribution of various stent strut geometries were studied. Results show strong correlations between the intra-stent hemodynamics and strut geometry. The intra-stent blood flow is very sensitive to the strut height and fillet size. A round strut with a large fillet size shows 36% and 34% reductions in key parameters evaluating the restenosis risk for the axisymmetric model and the 3-D stent model, respectively. This suggests that electrochemical polishing, a surface-improving process during stent manufacturing, strongly influences the hemodynamic behavior in stented arteries and should be controlled precisely in order to achieve the best clinical outcome. Rheological effects on the wall shear stress are minor in both axisymmetric and 3-D stent models for the vessel diameter of 4 mm, with Newtonian flow simulation tending to give more conservative estimates ofrestenosis risk. Therefore, it is reasonable to simulate the blood flow as a Newtonian flow in stented arteries using the simpler axisymmetric model. These findings will provide great insights for stent design optimization for potential restenosis improvement.
文摘Objective:Early detection of atherosclerotic renal artery stenosis (ARAS) is clinically important with respect to blood pressure control, prevention of renal insufficiency, and even improving survival. We investigated whether the presence of significant ARAS (luminal diameter narrowing ≥70%) could be predicted using a logistic regression model before coronary angiography/intervention. Methods:Initially, we developed a logistic regression model for detecting significant ARAS based upon clinical and angiographic features and biochemical measurements in a cohort of 1 813 patients undergoing transfemoral coronary and renal angiography. This model was then prospectively applied to an additional 495 patients who received transradial renal angiography to ascertain its predictive accuracy for the presence of significant ARAS. Results:Multivariate regression analysis revealed that older age (≥65 years), resistant hypertension, type 2 diabetes, creatinine clearance (Ccr) ≤60 ml/min, and multivessel coronary disease were independent predictors for significant ARAS. A logistic regression model for detecting ARAS by incorporating conventional risk factors and multivessel coronary disease was generated as:P/(1 P)=exp( 2.618+1.112[age≥65 years]+1.891[resistant hypertension]+0.453[type 2 diabetes]+0.587[Ccr≤60 ml/min]+2.254[multivessel coronary disease]). When this regression model was prospectively applied to the additional 495 patients undergoing transradial coronary and renal angiography, significant ARAS could be detected with a sensitivity of 81.2%, specificity of 88.9%, and positive and negative predictive accuracies of 53.8% and 96.7%, respectively. Conclusions:The logistic regression model generated in this study may be useful for screening for significant ARAS in patients undergoing transradial coronary angiography/intervention.
基金supported by the National Natural Science Foundation of China(81000125,81000127)Specialized Research Fund for the Doctoral Program of Higher Education(20100131120057)Promotive Research Fund for Young and Middle-aged Scientisits of Shandong Province(BS2012YY017)
文摘Complement component 5a(C5a)is a 74 amino acid glycoprotein and an important proinflammatory mediator that is cleaved enzymatically from its precursor,C5,on activation of the complement cascade.C5a is quickly metabolised by carboxypeptidases,forming the less-potent C5a desArg.C5a and C5a desArg interact with their receptors(C5aR and C5L2),which results in a number of effects which are essential to the immune response.C5a has a broad range of biological effects throughout the human body because the widespread expression of C5a receptors throughout the human organs enables C5a and C5a desArg to elicit a broad range of biological effects.Recently,accumulating evidence in humans and experimental animal models shows that the C5a-C5aR axis is involved in the development of atherosclerosis lesions.The absence or blockade of C5aRs greatly reduces the formation of atherosclerotic lesions or wire-injury-induced neointima formation in atherosclerosis-prone mice.Serum C5a level was related to the major adverse cardiovascular events in patients with advanced atherosclerosis and those with drug-eluting stent implantation.Thus,the C5a-C5aR axis may be a significant pathogenic driver of arteriosclerotic vascular disease,making C5a-C5aR inhibition an attractive therapeutic strategy.
文摘Objective: To observe the preventive role of Suxiao Jiuxin Pill (SX速效救心丸) on atherosclerosis (AS) and to probe into the mechanism in the atherosclerosis rat model. Methods: The AS rat model was established by a high fat diet and a large dose of calcium (vitamin D3, 0.6 million U/kg, i.p, once). Sixty healthy male adult Sprague-Dawlay (SD) rats were randomly divided into 6 groups, a normal control group (N), a model group (M), a SX low dose group (SXL), a SX middle dose group (SXM), a SX high dose group (SXH), and an atorvastatin group (ATO) (n=10 in each group). The rats in the treatment groups were given with the specific drugs from the first day by oral administration, and the normal control group and the model group were given with normal saline for 12 weeks. Afterwards, the content of malondialdehyde (MDA), the activity of superoxide dismutase (SOD) and the content of oxidized low density lipoprotein (ox-LDL) in the serum were detected. In addition, the expression of peroxisome proliferator-activated receptor γ (PPARγ) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) proteins were tested by Western-blot method. Results: The serum ox-LDL and MDA level significantly decreased, SOD activity increased in the SX middle, high dose groups and the atorvastatin group compared to the model group (all P<0.05). While the expression of PPARγ and NF-κb proteins significantly decreased in the SX low, middle, high dose groups and the atorvastatin group compared to the model group (all P<0.01), with the best effect in the SX high dose group .These results indicate that SX could elevate the activity of serum SOD, decrease serum level of MDA and ox-LDL, and reduce the expression of PPARγ and NF-κB proteins. Conclusion: SX plays an important role in anti-inflammation and inhibition of oxidative stress, which possibly are the mechanism of its preventing and treating atherosclerosis.
