高密度脂蛋白功能与心血管疾病

正常高密度脂蛋白(high-density lipoprotein,HDL)具有保护心血管的作用。但随着研究的深入,尤其是针对HDL代谢相关基因突变群体的研究和升高高密度脂蛋白胆固醇(high-density lipoprotein cholesterol, HDL-C)的药物研究失败后,HDL-C与心血管疾病的关系变得扑朔迷离。研究发现正常状态下HDL不仅有逆转运胆固醇(reverse cholesterol transport,RCT)的作用,还有抗氧化、抗炎、促进血管新生等作用,而疾病状态下HDL会失去保护作用甚至损害心血管功能。关于HDL的研究从HDL-C水平转移至HDL功能,失功能高密度脂蛋白(dysfunctional high-density lipoproteins, dHDL)假说逐渐被接受。随着基因测序和大数据理论的发展,更深入地研究HDL会给心血管领域带来新的曙光。     

好胆固醇受到重视

<正>胆固醇以2种形式运转于血液中:低密度脂蛋白胆固醇(LDL)和高密度脂蛋白胆固醇(HDL)。血液中胆固醇太多,LDL中的胆固醇开始附于动脉壁上,使动脉变硬,随时间推移,增加心血管危险。HDL的胆固醇似有相反的作用。HDL的颗粒装满了蛋白和脂肪。它摄取血中多余的胆固醇,运送至身体的其他部分,清除至体外。所以HDL保护个体不发生心血管病。为     

高密度脂蛋白及其亚类与冠状动脉疾病的关系

<正>研究发现,高密度脂蛋白(HDL)水平与动脉粥样硬化(AS)和冠心病(CHD)的发生、发展呈负相关,HDL在参与胆固醇逆向转运过程中,其组成、密度及颗粒大小均不断发生改变。近期研究表明,HDL对心血管的保护作用与血脂代谢过程中形成的HDL亚类在血中的相对含量、颗粒大小有关,HDL亚类组成异常可能与AS及CHD的发生发展密切相关。     

早期预警：氧化高密度脂蛋白—动脉粥样硬化的标志物？

高密度脂蛋白（HDL）具有两个重要作用,促进胆固醇逆转运和调节炎症。流行病学研究表明HDL水平与心血管事件发生的风险呈明显负相关,但许多发生心血管事件的患者,HDL水平正常,甚至升高。测定HDL水平只是反映HDL的量,而不能提供HDL的成分及功能信息。     

高密度脂蛋白功能改变可能是动脉粥样硬化形成的危险因素

高密度脂蛋白(HDL)是由1000多种脂质和几十种脂蛋白组成的复合体,因此,功能复杂、容易变异。正常HDL具有保护心血管的作用,可以抑制动脉粥样硬化形成。但近年来发现在某些疾病下,正常HDL可以转变为趋炎(或氧化)HDL,失去保护心血管的作用,甚损害心血管功能。因此,HDL可能成为心血管疾病的形成原因和治疗靶点。     

高密度脂蛋白胆固醇与动脉粥样硬化性心血管疾病

血高密度脂蛋白胆固醇(HDL-C)水平与动脉粥样硬化性心血管疾病(ASCVD)发生、发展相关,然而提高患者血浆HDL-C水平的药物未能降低ACSVD风险。研究发现,HDL-C亚类HDL3-C以及HDL-C的胆固醇外排能力(CEC)在ASCVD发生、发展过程中对心脏起重要保护作用,这为预测心血管事件风险及指导调脂治疗策略提供了新思路。     

血脂与动脉粥样硬化之间的关系:流行病学的证据和临床的联系

大规模的流行病学研究资料证实了总胆固醇、LDA 胆固醇的有害作用,HDL 胆固醇的保护作用,改变胆固醇比值、降压可降低冠心病的危险性。     

高密度脂蛋白功能改变对心血管疾病和围手术期心血管保护的影响

高密度脂蛋白(HDL)成分复杂,功能容易发生变异。正常HDL是一种保护性脂蛋白,有保护心血管的功能。但最近研究发现HDL成分和功能不但在冠心病、心脏瓣膜病变、动脉瘤、心功能不全等心血管疾病状态下发生改变,而且在心血管手术围手术期也发生改变。正常人的HDL趋炎指数很低,但心血管疾病状态下HDL趋炎指数变得很高,损伤血管内皮功能,影响心脏手术后血流动力学的稳定。载脂蛋白A-Ⅰ模拟肽、辛伐他汀等可部分改善HDL功能。如何改善HDL的功能,使其恢复保护心血管的作用,预防心血管疾病和增强围手术期心血管保护是将来的研究方向。     

原发性高胆固醇血症男性患者的日常体力活动和高密度脂蛋白胆固醇

人群的研究已经表明,高密度脂蛋白(HDL)胆固醇低下与冠心病危险性的增高有关,HDL 胆固醇高似乎具有保护作用。HDL 胆固醇与饮酒及体力活动呈正相关,而与吸烟、相对体重呈负相关。由于 HDL 胆固醇和甘油三酯间有复杂的相互联系,故体育活动与这些脂质指标之一的任何联系均需检验其与其他脂质指标的关系。本文调查7,106例年龄自35～59岁无症状的Ⅱ型高脂蛋白血症男性白人其日常体力活动与 HDL 胆固醇和甘油三酯之间的关系。旨在观察运动对这组冠心病危险性增高者的保护作用。方法:应用脂质调查门诊所的标准化方法测定     

高密度脂蛋白的抗血栓和促纤溶作用

越来越多的研究显示,血浆高密度脂蛋白(high density lipoprotein,HDL)及其载脂蛋白具有抗动脉粥样硬化和血管保护作用,据估计,血浆中的HDL浓度每升高10 mg/L,心血管事件的发生率要减少2%～3%[1].而其保护作用机制除了促进胆固醇逆转运、改善内皮功能、抗氧化、抗炎、清除毒性磷脂等之外,还包括抗血栓和促纤溶作用[2]J.HDL抗血栓形成的作用是通过阻止血小板和红细胞的聚集、减少血液黏滞度、抑制组织因子和纤溶酶原激活物抑制剂-1(plasminogen activatorinhibitor-1,PAI-1)的活性等方面来实现的.     

高密度脂蛋白亚类与心血管疾病的现状分析

高密度脂蛋白是一类异质性脂蛋白,其亚类表现出在抗动脉粥样硬化功能和心血管保护作用方面的差异性,并随年龄、性别等的差异也发生动态变化。影响高密度脂蛋白功能和亚类分布的药物或许是改善心血管风险更有效的方法。文章就高密度脂蛋白亚类的检测、抗动脉粥样硬化功能以及与心血管疾病的相关性等进行综述,为人类心血管疾病的防治提供新视角。     

“失功能”HDL与动脉粥样硬化

高密度脂蛋白(HDL)具有介导胆固醇逆向转运、抗氧化、抗炎、保护内皮等功能而被公认为动脉粥样硬化的重要防御因素。但在炎症、代谢性疾病状态下,HDL发生组分改变、氧化或修饰,可转化为致动脉粥样硬化的"失功能"HDL,进而与心血管事件发生率的增加有关。本文概述"失功能"HDL的组成与功能特征,旨在为动脉粥样硬化性心血管疾病提供新的诊治手段。     

Small LDL and its clinical importance as a new CAD risk factor: a female case study

The underlying metabolic cause of coronary heart disease in many patients is not high blood cholesterol. In fact, the Framingham study has reported that 80% of individuals who go on to have coronary artery disease have the same total blood cholesterol values as those who do not go on to have a cardiovascular event. The most common metabolic contributor to coronary artery disease is the atherogenic lipoprotein profile, characterized by an abundance of highly atherogenic small, dense low-density lipoprotein particles and a deficiency of the high-density lipoprotein (HDL) subtype most associated with coronary artery disease protection (HDL(2b)). This trait is present in 50% of men with coronary artery disease and is not reflected by total or low-density lipoprotein cholesterol values. While fasting triglycerides tend to he higher, and HDL cholesterol lower in patients with the atherogenic lipoprotein profile, the majority have triglyceride and HDL cholesterol values generally accepted to be in the "normal" range. An abundance of basic science and clinical trial evidence convincingly indicates that the presence of an atherogenic lipoprotein profile signifies a three-fold increased risk for a cardiovascular event and rapid arteriographic progression, but it also identifies a group of patients who respond particularly well to specific therapeutic interventions. Often the most effective interventions are the least expensive.     

HDL biogenesis and functions: Role of HDL quality and quantity in atherosclerosis

Coronary heart disease (CHD) is a leading cause of death in western societies. In the last few decades, a number of epidemiological studies have shown that a disproportion between atheroprotective and atherogenic lipoproteins in plasma is one of the most important contributors towards atherosclerosis and CHD. Thus, based on the classical view, reduced HDL cholesterol levels independently predict one's risk factor for developing cardiovascular disease, while elevated HDL levels protect from atherosclerosis. However, more recent studies have suggested that the relationship between HDL and cardiovascular risk is more complex and extends beyond the levels of HDL in plasma. These studies challenge the existing view on HDL and cardiovascular risk and trigger a discussion as to whether low HDL is a causal effect for the development of heart disease. In this article we provide a review of the current literature on the biogenesis of HDL and its proposed functions in atheroprotection. In addition, we discuss the significance of both HDL quality and quantity in assessing cardiovascular risk.     

High-density Lipoprotein

Epidemiological data clearly show an inverse relationship between high-density lipoprotein (HDL) cholesterol levels and cardiovascular risk. The HDL-mediated reverse cholesterol transport protects against atherosclerosis and raises the question whether therapeutic strategies to increase HDL levels can cause additional protection from coronary heart disease (CHD). The HDLs are a heterogeneous class of lipoproteins, the metabolism is complex and in certain aspects not well understood. This makes it impossible to predict whether a specific HDL intervention does actually protect against CHD. The currently used medications for raising HDL are fibrates and nicotinic acid; however, these drugs have additional effects on other lipoprotein classes and the benefits have not been finally proven in outcome studies. A promising possibility to raise HDL levels was thought to be the inhibition of cholesterol ester transfer protein (CETP); however, the first two substances tested, torcetrapib and dalcetrapib, failed to show a clinical benefit, and data for anacetrapib are not yet available. It is concluded that there is no proof of concept that therapeutic HDL elevation has a protective effect on cardiovascular events.     

Antioxidant vitamins and lipid therapy: end of a long romance?

During the past decade, the perception flourished that lipid and antioxidant therapy were 2 independent avenues for cardiovascular protection. However, studies have shown that commonly used antioxidant vitamin regimens do not prevent cardiovascular events. We found that the addition of antioxidant vitamins to simvastatin-niacin therapy substantially blunts the expected rise in the protective high density lipoprotein (HDL)2 cholesterol and lipoprotein(A-I) subfractions of HDL, with apparent adverse effects on the progression of coronary artery disease. To better understand this effect, 12 apolipoproteins, receptors, or enzymes that contribute to reverse cholesterol transport have been examined in terms of their relationship to HDL2 and lipoprotein(A-I) levels and the potential for antioxidant modulation of their gene expression. Three plausible candidate mechanisms are identified: (1) antioxidant stimulation of cholesteryl ester transfer protein expression/activity, (2) antioxidant suppression of macrophage ATP binding cassette transmembrane transporter A1 expression, and/or (3) antioxidant suppression of hepatic or intestinal apolipoprotein A-I synthesis or increase in apolipoprotein A-I catabolism. In summary, antioxidant vitamins E and C and beta-carotene, alone or in combination, do not protect against cardiovascular disease. Their use for this purpose may create a diversion away from proven therapies. Because these vitamins blunt the protective HDL2 cholesterol response to HDL cholesterol-targeted therapy, they are potentially harmful in this setting. We conclude that they should rarely, if ever, be recommended for cardiovascular protection.     

HDL对支架生物相容性的影响以及PCI术后HDL输注治疗的潜在价值

尽管介入技术与支架设计不断进步,但是支架生物相容性方面的问题仍然存在,包括支架内新生动脉粥样硬化和再内皮化延迟,这些问题会导致支架内再狭窄(ISR)和支架内血栓形成(ST).高密度脂蛋白(HDL)是一种重要的抗动脉粥样硬化因子,对动脉粥样硬化性心血管疾病(ASCVD)的患者具有保护作用.它能够维护血管内皮正常功能、保护...     

High-density lipoprotein and coronary heart disease – an update

There is increasing evidence for a protective effect of high density lipoprotein (HDL) on the cardiovascular system. Patients with low concentrations have been shown to be at an increased risk of coronary heart disease, and there is evidence that high concentrations confer a degree of protection. But there is uncertainty about when HDL should be measured, its role in the assessment of patients and its relative importance in making decisions about therapy. This review presents recent epidemiological findings and discusses the possible mechanisms of action of HDL. Insights from disease states are presented, and the results of intervention studies are discussed. Recent guidelines for the use of HDL in patient assessment are discussed, together with the options for therapy aiming to increase HDL concentrations. There are studies underway which should provide more information about the effects of current therapy, and perhaps lead to the development of new treatment options, and these are briefly summarised.     

HDL metabolism and the role of HDL in the treatment of high-risk patients with cardiovascular disease

Developing new therapeutic approaches to treating residual cardiovascular risk of recurrent clinical events in statin-treated patients has been a major challenge for the cardiovascular field. Data from epidemiological evidence, animal models, and initial clinical trials indicate that increasing high-density lipoprotein (HDL) may be an effective new target for treating residual cardiovascular risk. Over the past several years, major advances have occurred in our understanding of HDL metabolism and of the important roles of the ABCA1 and ABCG1 transporters as well as the SR-BI receptor in cholesterol transport. Current approaches to HDL therapy include acute HDL infusion therapy in acute coronary syndrome patients and chronic oral HDL therapy in stable patients with cardiovascular disease. Definitive clinical trials will now be required to establish the safety and efficacy of increasing HDL in the treatment of patients with cardiovascular disease.     

Apolipoprotein A-I and risk for cardiovascular diseases

Increased concentrations of high-density lipoprotein (HDL) cholesterol have been closely associated with decreased risk of future cardiovascular disease. This protective effect of HDL has been mainly attributed to its involvement in reverse cholesterol transport. More recently, it has been suggested that apolipoprotein A-I (apoA-I), the major protein component of HDL, possesses nearly identical information as HDL in terms of risk prediction for future cardiovascular disease. This makes apoA-I a very attractive biomarker candidate for implementation into clinical practice, taking into account its analytical advantages. This review summarizes our current knowledge based on observations from recent studies, with emphasis on potential pathophysiologic mechanisms of action and on the clinical utility of apoA-I as a predictor of cardiovascular risk.