Statins have been shown to be effective in reducing cardiovascular events.Their magnitude of benefits has been proportionate to the reduction in low-density lipoprotein cholesterol(LDL-c).Intensive lipid-lowering ther...Statins have been shown to be effective in reducing cardiovascular events.Their magnitude of benefits has been proportionate to the reduction in low-density lipoprotein cholesterol(LDL-c).Intensive lipid-lowering therapies using ezetimibe and more recently proprotein convertase subtilisin kexin 9 inhibitors have further improved clinical outcomes.Unselective application of these treatments is undesirable and unaffordable and,therefore,has been guided by LDL-c level.Nonetheless,the residual risk in the post-statin era is markedly heterogeneous,including thrombosis and inflammation risks.Moreover,the lipoprotein related risk is increasingly recognised to be related to other non-LDL-c markers such as Lp(a).Emerging data show that intensive lipid-lowering therapy produce larger absolute risk reduction in patients with polyvascular disease,post coronary artery bypass graft and diabetes.Notably,these clinical entities share similar phenotype of large burden of atherosclerotic plaques.Novel plaque imaging may aid decision making by identifying patients with propensity to develop lipid rich plagues at multi-vascular sites.Those patients may be suitable candidates for intensive lipid lowering treatment.展开更多
Objective:To study the value of serum PCSK9 for evaluating the severity in patients with type 2 diabetes mellitus and atherosclerosis. Methods:Type 2 diabetic patients with carotid atherosclerosis who were treated in ...Objective:To study the value of serum PCSK9 for evaluating the severity in patients with type 2 diabetes mellitus and atherosclerosis. Methods:Type 2 diabetic patients with carotid atherosclerosis who were treated in our hospital between May 2014 and September 2016 were selected as group A (n=69), type 2 diabetic patients without carotid atherosclerosis were selected as group B (n=79) and healthy subjects were selected as group C (n=55). Serum levels of SPCSK9, lipid metabolism indexes and oxidative stress indexes of three groups of subjects were detected. Results:Serum proprotein convertase subtilisin kexin 9 (PCSK9), triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (ApoB), CyPA, paraoxonase-1 (PON-1), PON-3, malondialdehyde (MDA) and 8-iso-prostaglandin F-2α(8-iso-PGF2α) levels of group A and group B were significantly higher than those of group C (P<0.05) while high-density lipoprotein cholesterol (HDL-C) and apolipoprotein AI (ApoAI) levels were significantly lower than those of group C (P<0.05);serum PCSK9, TG, TC, LDL-C, ApoB, CyPA, PON-1, PON-3, MDA and 8-iso-PGF2αlevels of group A were significantly higher than those of group B (P<0.05) while HDL-C and ApoAI levels were significantly lower than those of group B (P<0.05);serum TG, TC, LDL-C, ApoB, CyPA, PON-1, PON-3, MDA and 8-iso-PGF2αlevels of high PCSK9 level subgroup in group A were significantly higher than those of low PCSK9 level subgroup (P<0.05) while HDL-C and ApoAI levels were significantly lower than those of low PCSK9 level subgroup (P<0.05). Conclusions:Abnormally elevated serum PCSK9 can affect lipid metabolism and enhance oxidative stress in patients with type 2 diabetes mellitus and atherosclerosis.展开更多
Hyperlipidemia is a well-established risk factor for developing cardiovascular disease(CVD). The recent American College of Cardiology and American Heart Association guidelines on lipid management emphasize treatment ...Hyperlipidemia is a well-established risk factor for developing cardiovascular disease(CVD). The recent American College of Cardiology and American Heart Association guidelines on lipid management emphasize treatment of individuals at increased risk for developing CVD events with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors(statins) at doses proven to reduce CVD events. However, there are limited options for patients who are either intolerant to statin therapy, develop CVD despite being on maximally tolerated statin therapy, or have severe hypercholesterolemia. Recently the Food and Drug Administration approved two novel medications for low-density lipoprotein(LDL)-cholesterol reduction: Evolocumab and Alirocumab. These agents target and inactivate proprotein convertase subtilsinkexin type 9(PCSK9), a hepatic protease that attaches and internalizes LDL receptors into lysosomes hence promoting their destruction. By preventing LDL receptor destruction, LDL-C levels can be lowered 50%-60% above that achieved by statin therapy alone. This review explores PCSK-9 biology and the mechanisms available to alter it; clinical trials targeting PCSK9 activity, and the current state of clinically available inhibitors of PCSK9.展开更多
Objective:To investigate the effect of quercetin on ATP binding cassette transporter A1(ABCA1),liver X receptor(LXR),and proprotein convertase subtilisin/kexin type 9(PCSK9)expressions in apoE-knockout(ApoE-/-)mice.Me...Objective:To investigate the effect of quercetin on ATP binding cassette transporter A1(ABCA1),liver X receptor(LXR),and proprotein convertase subtilisin/kexin type 9(PCSK9)expressions in apoE-knockout(ApoE-/-)mice.Methods:The high-fat diet-induced atherosclerosis(AS)in ApoE-/-mice was established.Thirtysix mice were divided into 3 groups using random number table method:model group(n=12),quercetin group(n=12),and atorvastatin group(n=12),with C57BL/6J mice of the same strain and age as the control group(n=12).Quercetin group and atorvastatin group were administrated with quercetin and atorvastatin by oral gavage,with doses of 12.5 and 4 mg/(kg・d),respectively.Animals in the control and model groups were given an equal volume of distilled water by oral gavage once per day for a total of 12 weeks.Western blot and immunohistochemical methods were employed to determine the aortic ABCA1,LXR-a and PCSK9 protein expressi on.En zyme linked imm uno sorbent assay method was used to detect the expressi on of serum total cholesterol(TC),triglyceride(TG),high density lipoprotein-cholesterol(HDL-C),low density lipoproteincholesterol(LDL-C),tumor necrosis factor-a(TNF-a),interleukin-6(IL-6),and IL-10,combined with tissue pathological exami nation.Results:ApoE-/-mice fed with a high-fat diet had no table atherosclerosis lesions,with reduced ABCA1,LXR-a and IL-10 levels(all P<0.01),elevated PCSK9,TNF-a and IL-6 expression,and increased TC and LDL-C con tents(all P<0.01).After querceti n in terventi on,the areas of AS plaques and the expressions of PCSK9,TNF-a and IL-6 were significantly reduced(all P<0.01),while the expressions of ABCA1 and LXR-a were increased significantly(all P<0.01).Conclusion:Quercetin effectively interfered with AS development by regulating the expressions of ABCA1,LXR-a and PCSK9 in ApoE,mice.展开更多
2015年,前蛋白转化酶枯草杆菌蛋白酶/kexin 9(proprotein convertase subtilisin kexin 9,PCSK9)抑制剂依洛尤单抗被美国食品药品监督管理局(the Food and Drug Administration,FDA)批准上市,为高脂血症及心血管高危患者的治疗带来了新...2015年,前蛋白转化酶枯草杆菌蛋白酶/kexin 9(proprotein convertase subtilisin kexin 9,PCSK9)抑制剂依洛尤单抗被美国食品药品监督管理局(the Food and Drug Administration,FDA)批准上市,为高脂血症及心血管高危患者的治疗带来了新的希望。本文综述了依洛尤单抗的药学性质及相关临床试验结果,并介绍其在真实世界中的应用效果,以期为临床药物治疗提供参考。展开更多
文摘Statins have been shown to be effective in reducing cardiovascular events.Their magnitude of benefits has been proportionate to the reduction in low-density lipoprotein cholesterol(LDL-c).Intensive lipid-lowering therapies using ezetimibe and more recently proprotein convertase subtilisin kexin 9 inhibitors have further improved clinical outcomes.Unselective application of these treatments is undesirable and unaffordable and,therefore,has been guided by LDL-c level.Nonetheless,the residual risk in the post-statin era is markedly heterogeneous,including thrombosis and inflammation risks.Moreover,the lipoprotein related risk is increasingly recognised to be related to other non-LDL-c markers such as Lp(a).Emerging data show that intensive lipid-lowering therapy produce larger absolute risk reduction in patients with polyvascular disease,post coronary artery bypass graft and diabetes.Notably,these clinical entities share similar phenotype of large burden of atherosclerotic plaques.Novel plaque imaging may aid decision making by identifying patients with propensity to develop lipid rich plagues at multi-vascular sites.Those patients may be suitable candidates for intensive lipid lowering treatment.
基金National Natural Science Foundation of China(81601373).
文摘Objective:To study the value of serum PCSK9 for evaluating the severity in patients with type 2 diabetes mellitus and atherosclerosis. Methods:Type 2 diabetic patients with carotid atherosclerosis who were treated in our hospital between May 2014 and September 2016 were selected as group A (n=69), type 2 diabetic patients without carotid atherosclerosis were selected as group B (n=79) and healthy subjects were selected as group C (n=55). Serum levels of SPCSK9, lipid metabolism indexes and oxidative stress indexes of three groups of subjects were detected. Results:Serum proprotein convertase subtilisin kexin 9 (PCSK9), triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (ApoB), CyPA, paraoxonase-1 (PON-1), PON-3, malondialdehyde (MDA) and 8-iso-prostaglandin F-2α(8-iso-PGF2α) levels of group A and group B were significantly higher than those of group C (P<0.05) while high-density lipoprotein cholesterol (HDL-C) and apolipoprotein AI (ApoAI) levels were significantly lower than those of group C (P<0.05);serum PCSK9, TG, TC, LDL-C, ApoB, CyPA, PON-1, PON-3, MDA and 8-iso-PGF2αlevels of group A were significantly higher than those of group B (P<0.05) while HDL-C and ApoAI levels were significantly lower than those of group B (P<0.05);serum TG, TC, LDL-C, ApoB, CyPA, PON-1, PON-3, MDA and 8-iso-PGF2αlevels of high PCSK9 level subgroup in group A were significantly higher than those of low PCSK9 level subgroup (P<0.05) while HDL-C and ApoAI levels were significantly lower than those of low PCSK9 level subgroup (P<0.05). Conclusions:Abnormally elevated serum PCSK9 can affect lipid metabolism and enhance oxidative stress in patients with type 2 diabetes mellitus and atherosclerosis.
文摘Hyperlipidemia is a well-established risk factor for developing cardiovascular disease(CVD). The recent American College of Cardiology and American Heart Association guidelines on lipid management emphasize treatment of individuals at increased risk for developing CVD events with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors(statins) at doses proven to reduce CVD events. However, there are limited options for patients who are either intolerant to statin therapy, develop CVD despite being on maximally tolerated statin therapy, or have severe hypercholesterolemia. Recently the Food and Drug Administration approved two novel medications for low-density lipoprotein(LDL)-cholesterol reduction: Evolocumab and Alirocumab. These agents target and inactivate proprotein convertase subtilsinkexin type 9(PCSK9), a hepatic protease that attaches and internalizes LDL receptors into lysosomes hence promoting their destruction. By preventing LDL receptor destruction, LDL-C levels can be lowered 50%-60% above that achieved by statin therapy alone. This review explores PCSK-9 biology and the mechanisms available to alter it; clinical trials targeting PCSK9 activity, and the current state of clinically available inhibitors of PCSK9.
基金Supported by the National Natural Science Foundation of China(No.81202731,81873348)the Shanghai Nature Science Fund(No.16ZR1433900)+1 种基金the Shanghai Health and Family Planning Commission Fund(No.201640217)Shanghai University of Traditional Chinese Medicine Graduate "Innovation Ability Training" Special Research Projects(No.Y201858)
文摘Objective:To investigate the effect of quercetin on ATP binding cassette transporter A1(ABCA1),liver X receptor(LXR),and proprotein convertase subtilisin/kexin type 9(PCSK9)expressions in apoE-knockout(ApoE-/-)mice.Methods:The high-fat diet-induced atherosclerosis(AS)in ApoE-/-mice was established.Thirtysix mice were divided into 3 groups using random number table method:model group(n=12),quercetin group(n=12),and atorvastatin group(n=12),with C57BL/6J mice of the same strain and age as the control group(n=12).Quercetin group and atorvastatin group were administrated with quercetin and atorvastatin by oral gavage,with doses of 12.5 and 4 mg/(kg・d),respectively.Animals in the control and model groups were given an equal volume of distilled water by oral gavage once per day for a total of 12 weeks.Western blot and immunohistochemical methods were employed to determine the aortic ABCA1,LXR-a and PCSK9 protein expressi on.En zyme linked imm uno sorbent assay method was used to detect the expressi on of serum total cholesterol(TC),triglyceride(TG),high density lipoprotein-cholesterol(HDL-C),low density lipoproteincholesterol(LDL-C),tumor necrosis factor-a(TNF-a),interleukin-6(IL-6),and IL-10,combined with tissue pathological exami nation.Results:ApoE-/-mice fed with a high-fat diet had no table atherosclerosis lesions,with reduced ABCA1,LXR-a and IL-10 levels(all P<0.01),elevated PCSK9,TNF-a and IL-6 expression,and increased TC and LDL-C con tents(all P<0.01).After querceti n in terventi on,the areas of AS plaques and the expressions of PCSK9,TNF-a and IL-6 were significantly reduced(all P<0.01),while the expressions of ABCA1 and LXR-a were increased significantly(all P<0.01).Conclusion:Quercetin effectively interfered with AS development by regulating the expressions of ABCA1,LXR-a and PCSK9 in ApoE,mice.
文摘2015年,前蛋白转化酶枯草杆菌蛋白酶/kexin 9(proprotein convertase subtilisin kexin 9,PCSK9)抑制剂依洛尤单抗被美国食品药品监督管理局(the Food and Drug Administration,FDA)批准上市,为高脂血症及心血管高危患者的治疗带来了新的希望。本文综述了依洛尤单抗的药学性质及相关临床试验结果,并介绍其在真实世界中的应用效果,以期为临床药物治疗提供参考。