HIV Disease and Impairement of High Density Lipoprotein Metabolism

HIV 疾病和高密度脂蛋白代谢受损

• 批准号: 8460738
• 负责人: MICHAEL Ilya BUKRINSKY
• 金额: $ 12.48万
• 依托单位: GEORGE WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-15 至 2015-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8460738
• 关键词: Address; Anti-Retroviral Agents; Antiatherogenic; Atherosclerosis; Basic Science; Biochemical Pathway; Blood; Cardiovascular Diseases; Cardiovascular system; Cholesterol Homeostasis; Clinical; Clinical Research; Development; Diabetes Mellitus; Disease; Dyslipidemias; Foundations; HIV; HIV Infections; HIV-1; Heart; High Density Lipoproteins; Immune; Immunologics; Impairment; In Vitro; Individual; Infection; Inflammatory Response; Investigation; Lipids; Lipoproteins; Measures; Mediating; Metabolic; Metabolic Marker; Metabolic Pathway; Metabolism; Modeling; Morbidity - disease rate; Outcome; Pathogenesis; Patients; Pharmaceutical Preparations; Plasma; Play; Prevention; Property; Prospective Studies; Protease Inhibitor; Proteins; Public Health; Research; Research Institute; Research Personnel; Risk; Role; Sampling; Site; Structure; Study Subject; Testing; Universities; Washington; high risk; lipid metabolism; programs; prospective; public health relevance; reverse cholesterol transport; treatment strategy

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.

描述（由申请人提供）：心血管疾病（CVD）对感染HIV感染的个体的总体发病率产生了重大贡献。流行病学和前瞻性的因素是Altersclosis的最强预测指标。血脂异常和细胞内胆固醇代谢的障碍者。 HIV感染患者的血脂异常主要归因于抗逆转录病毒药物，尤其是蛋白酶抑制剂，但导致血脂异常的特定机制尚未完全表征。关于HIV感染本身诱导的脂质代谢的变化，知之甚少。在此应用中，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）的新陈代谢和功能的变化，这是血液中与HIV-1感染和抗逆转录病毒药物相关的关键抗动脉粥样硬化脂蛋白。我们还将将这些变化与这些患者动脉粥样硬化进展的替代度量相关。体外研究将解决HIV介导的对HDL的影响的机制，提出了以下特定目的：。具体目的1：表征对动脉粥样硬化和代谢失调的影响OLHIV疾病。 。特定目的2：表征HIV疾病对HDL组成和结构的影响。 特定目的3：表征HIV疾病对HDL功能的影响。特定目的4：表征负责HDL代谢损害的细胞机制。 。该提案中描述的研究是一项多PIC计划，该计划将依靠临床心脏病学家，基础科学心血管研究人员和病毒学家的合作努力：乔治华盛顿大学，哈佛大学和面包师心脏和糖尿病研究所。 公共卫生相关性：拟议的研究与公共卫生高度相关，因为它调查了感染HIV受试者的高风险风险的原因。鉴于10-30％的HIV感染者提供了某种形式的心血管疾病的证据，而动脉粥样硬化是心血管疾病的主要根本原因，因此动脉粥样硬化成为HIV疾病的主要并发症之一。但是，尚未完全了解将HIV感染和抗HIV治疗与动脉粥样硬化发展的机制与动脉粥样硬化的发展相关，这使得拟议的研究在基础科学和临床研究中都非常重要。