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Inflammatory Pathogenesis of Coronary Atherosclerosis in HIV

HIV冠状动脉粥样硬化的炎症发病机制

基本信息

批准号：
8992823
负责人：
ROBERT G WEISS
金额：
$ 62.92万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-01 至 2018-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8992823
关键词：
AIDS/HIV problem Address Adipose tissue Anatomy Anti-Inflammatory Agents Anti-inflammatory Atherosclerosis Autoimmune Diseases Biological Markers Biology Blood Vessels Caliber Cardiovascular system Catheterization Cholesterol Chronic Disease Clinical Clinical Trials Colchicine Coronary Coronary Arteriosclerosis Coronary Vessels Coronary artery Data Development Disease Dose Double-Blind Method Evaluation Event Gout Guidelines HIV HIV Seropositivity HIV therapy Health Heart Diseases Hematological Disease Hypertension Image Immune Immune response Individual Inflammation Inflammation Mediators Inflammatory Intervention Intervention Studies Knowledge Laboratories Lung diseases Magnetic Resonance Imaging Measures Medical Methods National Heart, Lung, and Blood Institute Outcome Pathogenesis Pathway interactions Patients Pericarditis Peripheral Pharmaceutical Preparations Pharmacologic Substance Phase Placebo Control Play Population Process Randomized Recruitment Activity Recurrence Research Risk Risk Factors Role Safety Source Testing Time United States National Institutes of Health Vasomotor abstracting antiretroviral therapy base brachial artery cardiovascular disorder risk clinical practice clinically relevant cohort conventional therapy coronary computed tomography angiography endothelial dysfunction experience imaging modality immune function improved in vivo insight novel paracrine response treatment strategy working group

项目摘要

DESCRIPTION (provided by applicant): HIV positive (HIV+) people today experience an increasing burden of coronary artery disease (CAD). Although it has been postulated that increased inflammation interacts with traditional risk factors to accelerate atherosclerosis in HIV+ people, the importance of inflammation per se in the pathogenesis of CAD in HIV+ people is not known. This critical gap in knowledge about CAD pathogenesis was identified by the NHLBI Working Group on "Advancing HIV/AIDS Research in Heart, Lung, and Blood Diseases" last year and addressing it is important not only for our understanding of in vivo vascular biology in the setting of HIV but also for defining the role, if any, for anti-inflammatory approaches in altering CAD in HIV+ people. Anti-inflammatory strategies are associated with lower cardiovascular event rates in individuals with inflammatory autoimmune disease and are appealing in HIV+ populations but are not currently used in practice because of the lack of an established and easily obtained measure of the effect of inflammation on the processes which result in coronary atherosclerosis and because no clinical trial has established whether an anti-inflammatory strategy alone alters these processes. One such process is coronary endothelial dysfunction, which plays a pivotal role in the development, progression, and clinical manifestations of CAD, and is a marker for sub-clinical disease, an independent predictor of adverse cardiovascular events, and a potential target for medical interventions. We recently developed noninvasive, reproducible MRI-based methods to measure coronary endothelial function (CEF). We propose a placebo-controlled, double blind, single-center mechanistic trial to test the hypothesis that the anti-inflammatory approach, low dose colchicine (LDC), improves impaired local CEF in HIV+ people with subclinical CAD. The studies will provide novel much-needed mechanistic insight into the potential of anti-inflammatory strategies to reduce coronary endothelial dysfunction, which inflammatory biomarkers herald the CEF response, the relationship of CAD and CEF with epicardial adipose tissue (a purported local paracrine source of pro-inflammatory mediators), and whether a heterogeneous CEF response occurs with differential effects in more severely than mildly diseased coronary vessels, suggesting local anti-inflammatory effects. In addition to this novel mechanistic information, the findings will provide critical safety data on LDC in HIV+ people to guide larger multicenter outcomes trials on this clinically available pharmaceutical. (End of Abstract)