预防心脑血管疾病 必须调控好血脂 中国首个蔬菜胶丸“心力健”帮助您轻松调脂

管好"坏胆固醇"心脑自然安血液中的脂肪类物质,统称为血脂。血浆中的脂类包括胆固醇、甘油三酯、磷脂和非游离脂肪酸等,它们在血液中是与不同的蛋白质结合在一起,以"脂蛋白"的形式存在。其中,低密度脂蛋白被称为"坏胆固醇",因为它是引发各种心脑血管疾病的元凶。随着人们生活方式的改变,越来越多人的"坏胆固醇"等血脂水平都在升高。而当人体内"坏胆固醇"含量过多时,可深入动脉内皮,堆积形成动脉粥样硬化斑块,导致动脉血管狭窄甚至阻塞,诱发心脑血管疾病。更可怕的是,有些斑块还会     

冠状动脉粥样硬化斑块稳定性与血清CTRP9、APN水平的关系

<正>随着人们生活水平的提高,饮食习惯发生了很大变化,随之而来的健康问题越来越多,其中动脉粥样硬化(atherosclerosis,AS)就是常见的一种。动脉粥样硬化是大、中动脉内膜出现含胆固醇、类脂肪等的黄色物质,常导致血栓形成、供血障碍等。高血压致使血液冲击血管内膜,导致管壁增厚、管腔变细。管壁内膜受损后易为胆固醇、脂质沉积,加重了动脉粥样斑块的形成。其主要特点就是"稳定斑块"向"不稳定斑块"转变,最终造成严重的后果如急性心脑血管疾病发生[1]。本研究探讨AS斑     

防治脑卒中的关键是降低“坏”胆固醇水平

目前在中国，每一分钟约有5人发生脑卒中、3人死于脑卒中。“要有效地防治脑卒中，关键是积极降低血液中的坏胆固醇水平。”首都医科大学附属北京天坛医院副院长、神经内科主任王拥军日前在北京郑重地告诫公众。在由卫生部疾病预防控制局、卫生部新闻办公室、中国记协新闻办公室主办，辉瑞制药公司协办的中国健康知识传播激励计划防治血脂异常专家／媒体座谈会上，王拥军说，“坏”胆固醇是指低密度脂蛋白胆固醇，它在血管壁中沉积，会形成动脉粥样硬化斑块。这些斑块一旦破裂，将激活血液凝固系统，形成血栓，阻塞血管，导致心肌梗死或脑卒中等心脑血管疾病的发生。     

普罗布考(probucol)

[药理作用]① 通过降低胆固醇合成与促进胆固醇分解使血胆固醇与低密度脂蛋白降低,改变高密度脂蛋白亚型的性质和功能,使高密度脂蛋白胆固醇降低.② 通过抑制氧化低密度脂蛋白的形成( OX-LDL) ,阻止OX-LDL进入巨噬细胞形成泡沫细胞,延缓动脉粥样硬化斑块形成,消退已形成的动脉粥样硬化斑块. [体内过程]口服吸收不良...     

把斑块消灭在“萌芽”状态

很多医学专家把粥样硬化斑块比作人体内的“不定时炸弹”“隐形杀手”。很多人会有这样的疑问,人体为什么会出现粥样硬化斑块,这些斑块又是怎么形成的呢？“坏”胆固醇导致斑块形成人体的血液中含有一定量的脂质,如甘油三酯和胆固醇等,这些脂质的含量一旦增高就变成了血管中的“垃圾”。其中,被称为“坏”胆固醇的低密度脂蛋白胆固醇增高是导致斑块形成的主要原因。     

动脉粥样硬化的发病机制及治疗

动脉粥样硬化是引起冠心病、脑梗死、外周血管病等心脑血管疾病的主要原因,可能由环境因素、遗传因素以及易感基因病变等多因素导致。动脉粥样硬化的病变基础是脂质代谢障碍,其特点是脂质的积累、病变斑块的形成和动脉腔隙变窄,这些因素导致动脉供应的组织器官缺血或坏死。其中内皮细胞、血管平滑肌细胞、巨噬细胞、淋巴细胞等是动脉粥样硬化形成中牵涉的主要细胞,内皮细胞的作用主要是吞噬异物、细菌、坏死和衰老的组织,参与集体免疫活动,其损伤和功能性障碍是动脉粥样硬化形成的第一步;血管平滑肌细胞是构成血管壁组织结构及维持血管张力的主要细胞成分,其结构及功能的改变是导致高血压、动脉粥样硬化和血管成形术后狭窄等多种心血管病的病理学基础,受损的血管平滑肌合成表型进而形成纤维帽,斑块破裂的区域细胞数量减少将进一步导致动脉粥样硬化的形成;淋巴细胞参与机体免疫应答,当淋巴细胞促进炎症细胞因子的分泌时即形成动脉粥样硬化;单核细胞和巨噬细胞起源于骨髓髓系细胞,其中分化成熟后进入血液的为单核细胞,进入组织的转变为巨噬细胞。机体在生理情况下,动脉血液中的巨噬细胞相对较少,血管内皮损伤后,血液中的单核细胞穿过内皮间隙进入血管内膜,在内膜下转化为巨噬细胞,帮助清除侵入内膜下的脂质。而巨噬细胞通过清道夫受体将氧化的低密度脂蛋白胆固醇吞噬,并降解形成泡沫细胞,过多的泡沫细胞堆积在一起形成脂质条纹即脂纹脂斑,从而形成粥样斑块并最终导致急性心脑血管事件。动脉粥样硬化主要通过抗炎、抗氧化、保护内皮细胞、抑制平滑肌细胞增殖和迁移、抗血小板聚集及改善动脉僵硬度达到治疗的作用。抗动脉粥样硬化的药物包括他汀类、抗氧化类、抗血小板聚集类和抗高血压药物。综上所述,动脉粥样硬化存在多种发病机制,对其治疗药物进行探讨,为预防和治疗提供有效的帮助,药物的联合使用已经获得较好的治疗效果,但仍待进一步研究。     

降脂治疗的意义

高血脂可引起动脉粥样硬化,动脉硬化又可引起心肌梗死,脑卒中等一系列心脑血管的意外事件,这是许多人都皆知的道理,但是动脉粥样硬化的早期没有临床症状,因此许多人不重视高血脂症,包括我们不少非专业的医生,对高血脂症也淡然置之.当动脉硬化产生后果时再重视治疗,其时晚矣.降脂治疗仅仅为固定粥样斑块,防止斑块脱落再导致心脑血管意外事件,因此高血脂症的防治必须从早期开始.     

小檗碱联合他汀类药物治疗高脂血症的临床疗效和安全性研究与分析

动脉粥样硬化是心血管疾病(CVD)的主要发病因素[1]。动脉粥样硬化的风险因素,例如高胆固醇血症、糖尿病和动脉高血压均与内皮功能障碍有关。内皮功能障碍是CVD的早期病理学变化,导致斑块的发生发展[2]。内皮功能障碍会促炎症和促血栓形成,在动脉粥样硬化的发生发展中发挥了关键的作用。内皮细胞暴露于高胆固醇血症的关键事件为内皮细胞源性血管舒张因子(EDRF)释放减少[3],而降低胆固醇水平似乎有利于改善内皮细胞功能[4]。     

胆固醇栓塞综合征

胆固醇栓塞综合征是大动脉血管壁上动脉粥样硬化斑块破裂,斑块内胆固醇结晶脱落至远端小动脉造成栓塞而引起的。胆固醇栓塞综合征常引起栓塞部位的炎症反应,并造成终末靶器官的损伤。最常受累的靶器官为脑、肾、消化道、皮肤和下肢骨骼肌等。诊断须依据症状、体征和实验室检查(嗜酸粒细胞增多)。他汀类药物、抗血小板药物、在易损斑块处安放支架等是目前治疗胆固醇栓塞综合征的主要手段。     

“好胆固醇”有那么好吗

动脉粥样硬化是心脑血管最常见的疾病。研究证实,其发病与多种危险因素相关,其中血脂异常是导致动脉粥样硬化的最主要危险因素之一。那么什么是血脂异常呢?血脂异常主要表现为胆固醇异常,如低密度脂蛋白胆固醇(LDL-C)偏高、高密度脂蛋白胆固醇(HDL-C)偏低或甘油三酯(TG)偏高,3项中至少具备1项便可以称为血脂异常。其中,LDL-C通常被称为"坏胆固醇",因为它可以导致动脉粥样硬化、脑卒中、冠心病及外周血管疾病发     

Alcohol and cardiovascular disease: Still unresolved underlying mechanisms

Alcoholic (ethanol-containing) beverages are consumed by most societies in the world. Low-to-moderate levels of ethanol consumption have been shown to reduce the risk of cardiovascular diseases and atherosclerosis. The decreased risk is likely due to alcohol's favorable pleiotropic effects on lipids, adhesion molecules, platelet activation and oxidative stress. However, there is also an abundance of clinical, experimental and epidemiological evidence showing that chronic high-dose ethanol consumption increases mortality, cardiovascular complications and also the progression of atherosclerosis. This last phenomenon appears to be due to the metabolism of ethanol, that leads to the formation of acetaldehyde, which is oxidized to acetate, leading to the generation of reactive oxygen species (ROS) and a toxic effect of ethanol on the formation of the atherosclerosis plaque. We will here briefly review the mechanisms through which high intakes of ethanol induce the formation of atherosclerotic plaque, focusing on increased oxidative stress as the main underlying mechanism.     

Therapeutic approaches to drug targets in atherosclerosis

Non-communicable diseases such as cancer, atherosclerosis and diabetes are responsible for major social and health burden as millions of people are dying every year. Out of which, atherosclerosis is the leading cause of deaths worldwide. The lipid abnormality is one of the major modifiable risk factors for atherosclerosis. Both genetic and environmental components are associated with the development of atherosclerotic plaques. Immune and inflammatory mediators have a complex role in the initiation and progression of atherosclerosis. Understanding of all these processes will help to invent a range of new biomarkers and novel treatment modalities targeting various cellular events in acute and chronic inflammation that are accountable for atherosclerosis. Several biochemical pathways, receptors and enzymes are involved in the development of atherosclerosis that would be possible targets for improving strategies for disease diagnosis and management. Earlier anti-inflammatory or lipid-lowering treatments could be useful for alleviating morbidity and mortality of atherosclerotic cardiovascular diseases. However, novel drug targets like endoglin receptor, PPARα, squalene synthase, thyroid hormone analogues, scavenger receptor and thyroid hormone analogues are more powerful to control the process of atherosclerosis. Therefore, the review briefly focuses on different novel targets that act at the starting stage of the plaque form to the thrombus formation in the atherosclerosis.     

Effects on Coronary Atherosclerosis by Targeting Low-Density Lipoprotein Cholesterol with Statins

A correlation exists between circulating levels of low-density lipoprotein cholesterol (LDL-C) and risk of cardiovascular disease (CVD). Evidence from clinical trials indicates that reducing LDL-C levels can result in beneficial clinical outcomes in patients at risk of CVD and in high-risk patients with clinical symptoms of CVD. Lipid-lowering agents, of which HMG-CoA reductase inhibitors (statins) are the most effective, protect against the vascular changes seen in the development of atherosclerotic plaque formation. Clinical trials assessing the effects of statins on coronary atherosclerosis using quantitative coronary angiography or intravascular ultrasound showed that statins can reduce progression or even cause regression of atherosclerotic plaque. This improvement of vascular structure after statin treatment is correlated with reductions in LDL-C levels. This appears to be the principal mechanism by which statin therapy reduces cardiovascular risk, with emerging evidence for statin-mediated changes in high-density lipoprotein and C-reactive protein levels contributing to modification of the atherosclerotic plaque.     

Novel approaches to treating cardiovascular disease: lessons from Tangier disease

Atherosclerotic cardiovascular disease (CVD) remains the leading cause of morbidity and mortality in Western societies. Although cholesterol is a major CVD risk factor, therapeutic interventions to lower plasma cholesterol levels have had limited success in reducing coronary events. Thus, novel approaches are needed to reduce or eliminate CVD. A potential therapeutic target is a newly discovered ATP binding cassette transporter called ABCA1, a cell membrane protein that is the gateway for secretion of excess cholesterol from macrophages into the high density lipoprotein (HDL) metabolic pathway. Mutations in ABCA1 cause Tangier disease, a severe HDL deficiency syndrome characterised by accumulation of cholesterol in tissue macrophages and prevalent atherosclerosis. Studies of Tangier disease heterozygotes revealed that the relative activity of ABCA1 determines plasma HDL levels and susceptibility to CVD. Drugs that induce ABCA1 in mice increase clearance of cholesterol from tissues and inhibit intestinal absorption of dietary cholesterol. Thus, ABCA1-stimulating drugs have the potential to both mobilise cholesterol from atherosclerotic lesions and eliminate cholesterol from the body. By reducing plaque formation and rupture independently of the atherogenic factors involved, these drugs would be powerful agents for treating CVD.     

Vulnerable plaque and inflammation: potential clinical strategies

Although enormous progress has been made in the prevention and treatment of cardiovascular disease, it still remains the leading cause of death worldwide. During the last decades, advances in the understanding of the pathophysiology of vulnerable plaque progression, coupled with novel diagnostic and therapeutic approaches, created a new opportunity for progress against cardiovascular disease. It has been demonstrated that inflammation, implicated in all stages of atherosclerosis, is an integral part of vulnerable plaque development and progression, leading eventually to plaque instability. Thus, new diagnostic modalities have been proposed for the detection of local plaque inflammation. Moreover, treatments such as stenting, photodynamic therapy, and novel pharmaceutical agents are under consideration as methods to stabilize the vulnerable plaques by inhibiting inflammation. This review provides an overview of the inflammatory process leading to atherosclerotic cardiovascular disease and the potential clinical strategies that may substantially decrease the incidence of events. We will mention the major impact of local and systemic inflammation on plaque advancing and destabilization, the imaging techniques for early detection of vulnerable plaques and the potential therapeutic strategies.     

胆固醇合成抑制剂抗动脉粥样硬化研究进展

胆固醇是形成动脉粥样硬化的主要原因之一,通过抑制体内胆固醇的生物合成,可以有效地减少动脉硬化的形成,进而有效地减少因动脉粥样硬化引起的血栓、纤维组织增生以及钙质沉着。目前,胆固醇合成抑制剂是一类重要的抗动脉粥样硬化药物,本文对抑制胆固醇生物合成中所需要的4种主要生物酶抑制剂的研究进展进行综述。     

甘草查尔酮B减轻高胆固醇饮食诱导的动脉粥样硬化

目的：探讨甘草查尔酮B是否能改善动脉粥样硬化。方法：采用高胆固醇饲料（HCD）喂食斑马鱼,建立斑马鱼动脉粥样硬化模型,并使用0.1 mg·L^-1和1 mg·L^-1甘草查尔酮B进行治疗。使用Tg （fli1a：EGFP）斑马鱼幼鱼构建模型,并向饲料中添加10 ng·g^-1橙色荧光标记的胆固醇,荧光显微镜检测斑马鱼血管中胆固醇蓄积。试剂盒检测LDL-C含量。分别使用Tg （lyz：DsRED2）和Tg （mpx：EGFP）和斑马鱼幼鱼构建模型,荧光显微镜检测斑马鱼血管中巨噬细胞浸润和中性粒细胞蓄积。HE染色和EVG染色检测斑马鱼血管中斑块形成的情况。结果：甘草查尔酮B显著减轻动脉粥样硬化斑马鱼血管中的胆固醇蓄积、中性粒细胞聚集和巨噬细胞浸润,降低LDL-C的含量,改善脂质代谢紊乱,最终减轻血管中的斑块形成。结论：甘草查尔酮B可有效减轻HCD诱导的动脉粥样硬化。     

Varenicline aggravates atherosclerotic plaque formation in nicotine-pretreated ApoE knockout mice due to enhanced oxLDL uptake by macrophages through downregulation of ABCA1 and ABCG1 expression

Varenicline is a widely used and effective drug for smoking cessation. We previously reported that varenicline aggravates atherosclerosis in apolipoprotein E knockout (ApoE KO) mice. However, it remains unknown whether varenicline affects cardiovascular events in patients with nicotine addiction. Here, we examined the effect of varenicline on atherosclerotic plaque formation in nicotine-pretreated ApoE KO mice and oxidized low-density lipoprotein (oxLDL) uptake in nicotine-treated peritoneal macrophages. Varenicline caused significant progression of plaque formation in the whole aorta and aortic root and further accelerated the increased formation of a macrophage-rich plaque area in the aortic root in nicotine-pretreated ApoE KO mice. Varenicline (10 μM) enhanced oxLDL uptake in peritoneal macrophages. Furthermore, this treatment significantly further lowered the decreased protein levels of ATP-binding cassette (ABC) transporter without affecting the expression of scavenger receptors LOX-1 and CD36 in RAW264.7 cells treated with 100 nM nicotine. Varenicline enhanced nicotine-induced oxLDL uptake in macrophages through decreased expression of cholesterol efflux transporters ABCA1 and ABCG1 and thereby progressed atherosclerotic plaque formation. Taken together, we tentatively conclude that nicotine exposure before and/or during varenicline treatment can aggravate varenicline-increased atherosclerotic plaque formation and progression. Therefore, this enhanced risk requires special consideration when prescribing varenicline to smoker patients.     

GYY4137 exhibits anti-atherosclerosis effect in apolipoprotein E (−/−) mice via PI3K/Akt and TLR4 signalling

Hydrogen sulphide (H₂S) had been suggested to be involved in the pathogenesis of atherosclerosis, but the underlying molecular mechanisms are poorly understood. In this study, we aimed to investigate the anti-atherosclerosis effect of morpholin-4-ium-methoxyphenyl-morpholino-phosphinodithioate (GYY4137) in RAW264.7 cell-derived foam cells formation and in the atherosclerotic plaque of ApoE−/− mice fed with a high-fat diet, and study the underlying mechanisms of phosphatidylinositol 3-kinase (PI3K), serine/ threonine kinase (Akt) and Toll-like receptor 4 (TLR4) signalling pathway. In the ApoE−/− mice fed with a high-fat diet, daily GYY4137 administration for 8 weeks effectively decreased carotid atherosclerotic plaque area and the volume of foam cells, regulated the lipid metabolism, down-regulated the pro-inflammatory cytokine levels and up-regulated the anti-inflammatory cytokines levels. Consistent with these findings, in the RAW264.7 cell-derived foam cells, GYY4137 ameliorated foam cell formation in vitro, and decreased the expression of pro-inflammatory cytokines. Furthermore, our studies showed that GYY4137 could activate the PI3K/Akt signalling pathway and consequently reduce the expression of TLR4 to be critical for foam cell formation, preventing atherosclerotic plaque formation and destabilization. LY294002, a PI3K inhibitor, could inhibit the phosphorylation of Akt and reduce the expression of TLR4, thus reduce the foam cell source and lipid volume in the unstable plaque tissue. Our results suggest that GYY4137 is an attractive novel therapeutic reagent for atherosclerosis diseases. This mechanism may be partially attributed to regulating the PI3K/Akt/TLR4 signalling pathway.