Atherosclerosis and Inflammation in HIV Disease

HIV 疾病中的动脉粥样硬化和炎症

基本信息

批准号：
7494828
负责人：
Janet Lo
金额：
$ 13.99万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-09-02 至 2013-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7494828
关键词：
Adipose tissue Age Angiography Anti-Retroviral Agents Arterial Fatty Streak Atherosclerosis Attenuated Biology Biometry C-reactive protein CD4 Positive T Lymphocytes CD8-Positive T-Lymphocytes CD8B1 gene Cardiac Cardiology Cardiovascular Diseases Cardiovascular system Categories Cells Cholesterol Chronic Coenzyme A Combined Modality Therapy Communities Coronary Coronary Arteriosclerosis Cytotoxic T-Lymphocytes Development Diabetes Mellitus Discipline Disease Drug or chemical Tissue Distribution Dyslipidemias End Point Endocrinology Environment Event Excess Mortality Fatty acid glycerol esters Future General Population Glucose Metabolism Disorders Goals Grant HIV HIV Infections Health Services Accessibility Hyperinsulinism Image Immune System Diseases Individual Infection Inflammation Inflammatory Insulin Resistance Interferons K-Series Research Career Programs Lead Link Measures Medicine Mentors Mentorship Metabolic Oxidoreductase Patients Physiological Placebo Control Placebos Play Population Pravastatin Prevalence Prevention Prevention strategy Production Randomized Recruitment Activity Research Research Personnel Risk Risk Factors Role Slice Smoking T-Cell Activation T-Lymphocyte T-Lymphocyte Subsets Translational Research Virus Diseases Visceral X-Ray Computed Tomography abstracting blood glucose regulation burden of illness cardiovascular risk factor career cohort day design detector fluorodeoxyglucose positron emission tomography immune function improved inhibitor/antagonist monocyte novel patient oriented prevent programs response skills transcription factor

项目摘要

DESCRIPTION (provided by applicant): Survival of HIV-infected patients worldwide has remarkably improved with the use of anti-retroviral therapy. Metabolic and cardiovascular complications associated with HIV infection and its treatment are becoming more evident as this patient population ages with chronic viral infection. Metabolic and inflammatory changes in HIV-infected patients including dyslipidemia, insulin resistance, fat redistribution with abnormal adipocytokine secretion, alterations in monocyte subsets, and T-cell activation may increase the risk of atherosclerotic disease. The aims of the proposed grant are: 1) to determine the prevalence and degree of subclinical coronary atherosclerosis using CT angiography in patients with HIV compared to agematched control subjects without HIV infection, 2) to examine risk factors for coronary atherosclerosis in HIV patients, specifically evaluating the potential roles of adipocytokines, monocyte subsets, and T cell activation in atherosclerosis development, and 3) to perform a randomized, placebo-controlled, physiologic study in HIV patients with subclinical coronary atherosclerosis comparing the effects of statin therapy vs. placebo on plaque inflammation (as determined by 18F-fluorodeoxyglucose positron emission tomography), inhibition of plaque progression (as determined by coronary CT angiography), monocyte subsets and T cell response. Characterization of the atherosclerotic disease burden as well as identification of risk factors associated with atherosclerotic disease in HIV will be instrumental to guide the future design of appropriate prevention and treatment strategies for the HIV patient population. To achieve these aims, the candidate will be mentored by internationally recognized experts from several relevant disciplines in patient-oriented and translational research, endocrinology, cardiology, inflammation biology, HIV medicine, cardiac imaging, and biostatistics. Their mentorship and the strength of the candidate's institutional support will provide a well-suited academic environment to conduct this research and to nurture the candidate's career development. This K23 career development award will help the candidate to acquire the additional research skills to achieve her goal of becoming an independent patientoriented translational investigator. (End of Abstract)

描述（由申请人提供）：通过使用抗逆转录病毒疗法，全世界艾滋病毒感染者的生存率显着提高。随着慢性病毒感染患者群体的老龄化，与艾滋病毒感染及其治疗相关的代谢和心血管并发症变得越来越明显。 HIV感染者的代谢和炎症变化，包括血脂异常、胰岛素抵抗、脂肪细胞因子分泌异常的脂肪重新分布、单核细胞亚群的改变和T细胞激活，可能会增加动脉粥样硬化疾病的风险。拟议拨款的目的是：1) 使用 CT 血管造影确定 HIV 患者与年龄匹配的未感染 HIV 的对照受试者相比，亚临床冠状动脉粥样硬化的患病率和程度，2) 检查 HIV 患者冠状动脉粥样硬化的危险因素，特别是评估脂肪细胞因子、单核细胞亚群和 T 细胞激活在动脉粥样硬化发展中的潜在作用，以及 3) 进行随机、安慰剂对照、生理学研究在患有亚临床冠状动脉粥样硬化的 HIV 患者中进行的研究，比较了他汀类药物治疗与安慰剂对斑块炎症（通过 18F-氟脱氧葡萄糖正电子发射断层扫描确定）、斑块进展抑制（通过冠状动脉 CT 血管造影确定）、单核细胞亚群和 T 细胞的影响回复。动脉粥样硬化疾病负担的表征以及与艾滋病毒动脉粥样硬化疾病相关的危险因素的识别将有助于指导未来为艾滋病毒患者群体设计适当的预防和治疗策略。为了实现这些目标，候选人将接受来自以患者为导向的转化研究、内分泌学、心脏病学、炎症生物学、艾滋病毒医学、心脏成像和生物统计学等多个相关学科的国际公认专家的指导。他们的指导和候选人的机构支持将为开展这项研究和培养候选人的职业发展提供一个非常合适的学术环境。该 K23 职业发展奖将帮助候选人获得额外的研究技能，以实现成为一名独立的以患者为导向的转化研究者的目标。（摘要完）