HIV Viral Reservoirs and Monocyte Activation in HIV-Associated Atherosclerosis

HIV 相关动脉粥样硬化中的 HIV 病毒库和单核细胞激活

• 批准号: 8731047
• 负责人: Priscilla Y. Hsue
• 金额: $ 18.15万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-03-01 至 2019-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8731047
• 关键词: Adult; Animal Model; Anti-Retroviral Agents; Arterial Fatty Streak; Atherosclerosis; Blood Vessels; CD4 Positive T Lymphocytes; Cardiology; Cardiovascular Diseases; Cardiovascular system; Carotid Arteries; Cell Count; Chronic; Clinic; Clinical; Clinical Research; Collaborations; Complex; Coronary Arteriosclerosis; Cytomegalovirus; Data; Development; Disease; Endothelium; Face; Functional disorder; Funding; Future; General Hospitals; General Population; HIV; HIV Infections; HIV-1; Health; Image; Immunologic Deficiency Syndromes; Individual; Infection; Inflammation; Inflammatory; Interleukin-6; Intervention; Investigation; Laboratories; Link; Macrophage Activation; Measurement; Measures; Mediating; Mentors; Microvascular Dysfunction; Mid-Career Clinical Scientist Award (K24); Modeling; Pathogenesis; Patients; Pharmaceutical Preparations; Play; Population; RNA; Research; Research Infrastructure; Research Personnel; Resources; Risk; Risk Factors; Role; San Francisco; Series; T-Cell Activation; Testing; Thick; Time; Translational Research; United States National Institutes of Health; Vascular Diseases; Vasodilation; Viral; Visit; Work; brachial artery; cardiovascular risk factor; career; cohort; design; endothelial dysfunction; immune activation; improved; inflammatory marker; intima media; macrophage; monocyte; novel; patient oriented; public health relevance; sudden cardiac death

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.

描述（由申请人提供）：Hsue博士是世界上为数不多的具有广泛研究和艾滋病毒临床专业知识的心脏病学家之一，并且在过去的十年中研究了艾滋病毒的心血管疾病。她职业生涯的最初部分花在了1）在旧金山综合医院（SFGH）建立HIV心脏病学诊所，2）开发基础设施，以在SFGH的心脏病学部门进行POR研究，其中包括开发用于临床研究的血管实验室，以及3）进行研究，以评估研究机制，以评估HISLY HISNING HISNING HISTINE INDENING HASISINING INSUCTIAN INDENING SUNDENING HASIS IFTIVEDION和CARDISIESICASICASICASSICASICASS（CODISICASICASICASSIFURCAL和CARDISICASICASICASTAIL）（CVD）。她工作的发现表明，1）HIV感染与CVD独立相关，与传统危险因素或HIV药物无关，以及2）在有效治疗的HIV感染的情况下，慢性炎症是这种增加的CV风险，并且3）识别疗法以减少与HIV相关的炎症和CV风险。对于她的5年K24奖项提案，她计划增加在艾滋病毒感染，艾滋病毒相关炎症和心血管疾病领域指导初级调查人员花费的时间，以帮助他们将来成为成功的独立研究人员。 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通过在有效治疗的受HIV感染的个体中，通过流动介导的臂动脉（FMD）和微血管疾病（通过高血症速度）的血管舒张（通过峰值测量）确定HIV储层对动脉粥样硬化进展，对动脉粥样硬化进展，内皮性疾病的作用，在有效治疗的HIV受HIV中受到治疗。 K24提案将提供主题访问，血管成像以及临床和实验室数据，以支持在与HIV相关的心血管疾病领域的患者转化研究中指导新研究者。