HIV Viral Reservoirs and Monocyte Activation in HIV-Associated Atherosclerosis

描述（由申请人提供）：徐博士是世界上少数几个心脏病专家之一，在艾滋病毒方面具有广泛的研究和临床专业知识，并在过去十年中致力于研究艾滋病毒背景下的心血管疾病。她职业生涯的最初部分是1）在弗朗西斯科总医院（SFGH）建立艾滋病毒心脏病诊所，2）开发基础设施，在SFGH心脏病科进行POR研究，其中包括开发用于临床研究的血管实验室，3）进行研究，评估艾滋病毒感染和心血管疾病（CVD）的潜在机制。她的研究结果表明：1）HIV感染与CVD独立相关，独立于传统的风险因素或HIV药物，2）在有效治疗HIV感染的情况下慢性炎症是CV风险增加的基础，3）确定减少HIV相关炎症和CV风险的疗法。对于她的5年K24奖提案，她计划增加她在艾滋病毒感染，艾滋病毒相关炎症和心血管疾病领域指导初级研究人员的时间，以帮助他们在未来成为成功的独立研究人员。她的K24提案将在她目前的R 01资助的研究基础上进行扩展，研究在治疗HIV感染的背景下HIV相关动脉粥样硬化的潜在机制，具体目标如下：1）表征单核细胞/巨噬细胞活化在动脉粥样硬化进展中的作用，如通过颈动脉内膜中层厚度（IMT）评估的，通过肱动脉（FMD）的血流介导的血管舒张评估的内皮功能障碍和微血管疾病（通过峰值充血速度测量）2）为了确定HIV储库在动脉粥样硬化进展中的作用，内皮功能和微血管疾病。K24提案将提供受试者访视、血管成像以及临床和实验室数据，以支持指导新的研究人员在艾滋病毒相关心血管疾病领域进行以患者为导向的转化研究。

DESCRIPTION (provided by applicant): Dr. Hsue is one of the few cardiologists in the world with both extensive research and clinical expertise in HIV and has devoted the last ten years studying cardiovascular disease in the setting of HIV. The initial part of her career was spent 1) establishing a HIV Cardiology Clinic at San Francisco General Hospital (SFGH), 2) developing the infrastructure to perform POR research in the Cardiology Division at SFGH which has included development of a vascular laboratory for clinical research, and 3) performing studies that evaluate the mechanisms underlying HIV infection and cardiovascular disease (CVD). The findings from her work have shown that 1) HIV infection is independently associated with CVD, independent of traditional risk factors or HIV medication, and 2) chronic inflammation in the setting of effectively treated HIV infection underlies this increased CV risk, and 3) identifying therapies to reduce HIV-associated inflammation and CV risk. For her 5 year K24 award proposal, she plans to increase her time spent mentoring junior investigators in the fields of HIV infection, HIV-associated inflammation, and cardiovascular disease for the purpose of helping them to become successful independent researchers in the future. Her K24 proposal will extend upon her current R01 funded investigations by studying the underlying mechanism of HIV-associated atherosclerosis in the setting of treated HIV infection with the following two Specific Aims: 1) To characterize the role of monocyte/macrophage activation in atherosclerotic progression as assessed by carotid artery intima-media thickness (IMT), endothelial dysfunction as assessed by flow-mediated vasodilation of the brachial artery (FMD), and microvascular disease (measured by peak hyperemic velocity) in effectively treated HIV-infected individuals 2) To determine the role of HIV reservoir on atherosclerotic progression, endothelial function, and microvascular disease in effectively treated HIV-infected individuals. The K24 proposal will provide subject visits, vascular imaging, and clinical and laboratory data to support mentoring new investigators in patient-oriented translational research in the field of HIV-related cardiovascular disease.