HDL-apoA-I exchange: rapid detection and association with atherosclerosis.

HDL-apoA-I exchange: rapid detection and association with atherosclerosis.
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DOI:
10.1371/journal.pone.0071541
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Oda MN
Oda MN
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Borja MS;Zhao L;Hammerson B;Tang C;Yang R;Carson N;Fernando G;Liu X;Budamagunta MS;Genest J;Shearer GC;Duclos F;Oda MN

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高密度脂蛋白(HDL)胆固醇水平与心血管疾病风险降低相关,但并非所有HDL在功能上都是等效的。HDL功能状态的主要决定因素是其主要蛋白组分apoA-I(可交换的载脂蛋白)的构象适应性。apoA-I的化学修饰,如在炎症或糖尿病条件下可能发生的,可严重损害HDL功能,并与心血管疾病的存在相关。apoA-I的化学修饰也削弱了其交换HDL的能力,这是胆固醇逆向转运的关键过程。在这项研究中,我们开发了一种方法,使用电子顺磁共振光谱(EPR)定量HDL-apoA-I交换。使用这种方法,我们测量了HDL-apoA-I与HDL的交换程度,这些HDL是从喂食高脂肪、高胆固醇饮食的兔子以及患有急性冠脉综合征和代谢综合征的人类受试者中分离出来的。我们观察到,HDL-apoA-I交换显着减少时,动脉粥样硬化的存在,或当受试者携带至少一个心血管疾病的危险因素。这些结果表明HDL-apoA-I交换是与心血管疾病相关的HDL功能的临床相关测量。
High density lipoprotein (HDL) cholesterol levels are associated with decreased risk of cardiovascular disease, but not all HDL are functionally equivalent. A primary determinant of HDL functional status is the conformational adaptability of its main protein component, apoA-I, an exchangeable apolipoprotein. Chemical modification of apoA-I, as may occur under conditions of inflammation or diabetes, can severely impair HDL function and is associated with the presence of cardiovascular disease. Chemical modification of apoA-I also impairs its ability to exchange on and off HDL, a critical process in reverse cholesterol transport. In this study, we developed a method using electron paramagnetic resonance spectroscopy (EPR) to quantify HDL-apoA-I exchange. Using this approach, we measured the degree of HDL-apoA-I exchange for HDL isolated from rabbits fed a high fat, high cholesterol diet, as well as human subjects with acute coronary syndrome and metabolic syndrome. We observed that HDL-apoA-I exchange was markedly reduced when atherosclerosis was present, or when the subject carries at least one risk factor of cardiovascular disease. These results show that HDL-apoA-I exchange is a clinically relevant measure of HDL function pertinent to cardiovascular disease.
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