HIV Disease and Impairement of High Density Lipoprotein Metabolism

描述（由申请人提供）：心血管疾病（CVD）是艾滋病毒感染者总体发病率的重要因素。这些因素在流行病学和前瞻性上都是最强的预测因子。动脉粥样硬化是血脂异常和细胞内胆固醇代谢受损。hiv感染患者的血脂异常主要归因于抗逆转录病毒药物，特别是蛋白酶抑制剂，但导致血脂异常的具体机制尚未完全确定。关于HIV感染本身引起的脂质代谢的变化，我们所知的就更少了。在这项应用中，我们提出了一项针对hiv感染患者的前瞻性研究，以表征高密度脂蛋白（HDL）代谢和功能的变化，高密度脂蛋白是血液中关键的抗动脉粥样硬化脂蛋白，与HIV-1感染和抗逆转录病毒药物相关。我们还将这些变化与这些患者动脉粥样硬化进展的替代测量相关联。体外研究将探讨hiv介导对HDL的影响机制。特异性目的1：表征oLHIV疾病对动脉粥样硬化和代谢失调的影响。特异性目的2：表征HIV疾病对HDL组成和结构的影响。特异性目的3：表征HIV疾病对HDL功能的影响。特异性目的4：表征HDL代谢损伤的细胞机制。本提案中所描述的研究是一个mUlti-PI项目，将依赖于临床心脏病学家、基础科学心血管研究人员和病毒学家在三个地点的合作努力：乔治华盛顿大学、哈佛大学和贝克尔迪心脏与糖尿病研究所。

DESCRIPTION (provided by applicant): Cardiovascular disease (CVD) contributes substantially to the overall morbidity of HIV-infected individuals. Factors that epidemiologically and prospectively are the strongest predictors of .atherosclerosis are dyslipidemia and impairmen of intracellular cholesterol metabolism. Dyslipidemia in HIV-infected patients has been attributed mainly to antiretroviral drugs, in particular protease inhibitors, but specific mechanisms responsible for dyslipidemia have not been fully characterized. Even less is known about changes in lipid metabolism induced by HIV infection itself. In this application we propose a prospective study with HIV-infected patients to characterize changes in metabolism and functionality of High Density Lipoprotein (HDL), the key anti-atherogenic lipoprotein in the blood, associated with HIV-1 infection and anti-retroviral drugs. We will also correlate these changes with the surrogate measures of progression of atherosclerosis in these patients. Studies in vitro will address the mechanism of HIV-mediated effect on HDL The following Specific Aims are proposed: . Specific Aim 1: To characterize effects oLHIV disease on atherosclerosis and metabolic dysregulation. . Specific Aim 2: To characterize the effect of HIV disease on HDL composition and structure. Specific Aim 3: To characterize effects of HIV disease on HDL functionality. Specific Aim 4: To characterize cellular mechanisms responsible for impairment of HDL metabolism. . Research described in this proposal is a mUlti-PI program that will rely on collaborative efforts of clinical cardiologists, basic science cardiovascular researchers and virologists at three sites: the George Washington University, Harvard University and BakerlDI Heart and Diabetes Research Institute. PUBLIC HEALTH RELEVANCE: The proposed research is highly relevant to Public Health as it investigates the reason for high risk of atherosclerosis in HIV-infected subjects. Given that 10-30% of HIV-infected individuals present evidence of some form of cardiovascular disease, and atherosclerosis is the main underlying cause of cardiovascular disease, atherosclerosis becomes one of the main complications of HIV disease. However, mechanisms connecting HIV infection and anti-HIV treatment with development of atherosclerosis are not fully understood, making proposed study highly significant both for basic science and clinical research.