2型糖尿病患者HDL水平、结构、功能变化及其与动脉粥样硬化性心血管疾病的关系  

Changes of HDL level, structure and function in type 2 diabetes mellitus patients and its relationship with atherosclerotic cardiovascular disease

作　　者：王冲[1] 王贵松[1] WANG Chong;WANG Gui-song(Department of Cardiology,Peking University Third Hospital,NHFPC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides,Ministry of Health,Key Laboratory of Molecular Cardiovascular Sciences,Ministry of Education,Beijing 100191,China)

机构地区：[1]北京大学第三医院心内科国家卫生计生委心血管分子生物学与调节肽重点实验室分子心血管学教育部重点实验室,北京100191

出　　处：《中国医学前沿杂志（电子版）》2018年第2期26-32,共7页Chinese Journal of the Frontiers of Medical Science(Electronic Version)

摘　　要：2型糖尿病(type 2 diabetes mellitus,T2DM)是动脉粥样硬化性心血管疾病(atherosclerotic cardiovascular disease,ASCVD)的独立危险因素,可引起或加重ASCVD。目前认为,ASCVD是T2DM患者的首要死亡原因。流行病学研究显示,高密度脂蛋白胆固醇(high-density lipoprotein cholesterol,HDL-C)水平与心血管事件发生风险呈负相关,所以认为T2DM患者特征性的低HDL-C水平是导致其心血管事件发生率增加的重要危险因素之一。然而,最近几项通过胆固醇酯转移蛋白(cholesterol ester transfer protein,CETP)抑制剂提高HDL-C水平的临床试验发现,升高HDL-C水平并不能降低心血管事件的发生风险。随着研究的深入,人们认识到高密度脂蛋白(high-density lipoprotein,HDL)的功能相较于其水平高低的更加重要。高血糖诱导的糖基化终末产物增加、HDL相关蛋白糖基化、T2DM状态下氧化应激和慢性炎症造成HDL蛋白质组学和脂质组学改变等诸多因素导致HDL功能障碍,使HDL促胆固醇外流、抗氧化、抗炎等具有抗动脉粥样硬化作用的功能减弱,甚至转化为促动脉粥样硬化颗粒,进而导致ASCVD的发生和发展。本文就T2DM状态下HDL水平、结构、功能变化的机制及其与ASCVD的关系进行综述。Type 2 diabetes mellitus(T2DM)is an independent risk factor for atherosclerotic cardiovascular disease(ASCVD)and can cause or aggravate ASCVD.ASCVD is the leading cause of mortality in patients with T2DM.Epidemiological studies suggested inverse correlation between high-density lipoprotein cholesterol(HDL-C)and ASCVD occurrence.Therefore,low HDL-C concentration observed in T2DM patients was thought to be one of the primary causes of increased risks of cardiovascular events.However,recently efforts to raise HDL-C level via cholesterol ester transfer protein(CETP)inhibitors turned out to be disappointing in outcome studies despite substantial increases in HDL-C,suggesting that factors beyond high-density lipoprotein(HDL)concentration may be responsible for the increased risks of cardiovascular events.As the study progresses,it has been recognized that HDL functions are comparable to its level is more important.Hyperglycemia-induced advanced glycation end products and glycation of HDL-associated proteins,the metabolic environment in diabetes mellitus condition such as oxidative stress and inflammation results in major changes in the HDL proteome and lipidomics.Changes that not only devoid the HDL of its normal function,include cholesterol efflux,antioxidative and anti-inflammatory activities,but also turn it into a proatherogenic particle,and then promote the occurrence and development of ASCVD.This article reviews the mechanism of changes in HDL levels,structure,and function in relation to T2DM status and its relationship with ASCVD.

关 键 词：2型糖尿病 HDL功能障碍 氧化应激 糖基化 炎症 动脉粥样硬化 

分 类 号：R587.2[医药卫生—内分泌]