HIV Infection, Metabolites and Subclinical Atherosclerosis

 描述(由申请者提供)：这份K01职业发展奖申请书提出了一个为期4年的多学科培训计划，为候选人齐齐斌博士提供作为一名独立调查人员开始成功职业生涯所需的经验和资源。该培训计划是与主要导师卡普兰·罗伯特博士、共同导师凯瑟琳·阿纳斯托斯博士以及一个咨询委员会密切合作制定的，将扩大齐博士的研究经验和专业知识，包括代谢组学、生物统计学以及艾滋病毒感染和心血管疾病(CVD)流行病学。拟议的研究项目建立在两个具有良好特点的艾滋病毒队列研究(妇女机构间艾滋病毒研究[WIHS]和多中心艾滋病队列研究[MACS])的基础上，为候选人提供了精通代谢组学研究以及艾滋病毒感染和心血管疾病流行病学的新领域的绝佳机会。利用存档的血液样本、HIV感染相关因素的广泛数据、颈动脉斑块的纵向测量以及WIHS和MACS的基因组数据，该项目建议检测495名年龄=45岁、基线无颈动脉斑块的女性和男性的血浆代谢物水平(338名HIV和157名HIV受试者；103名受试者有7年以上的B型超声随访颈动脉斑块)。将研究HIV感染和相关因素与先前知情的心脏代谢相关代谢物(例如支链氨基酸)的相关性，以及这些代谢物与亚临床颈动脉粥样硬化(颈动脉斑块)进展的相关性。在探索性分析中，将应用先进的分析方法(如网络分析)来确定与艾滋病毒感染和亚临床动脉粥样硬化进展相关的新的代谢组特征，并生成一个网络，说明基因、代谢物、艾滋病毒感染和心血管疾病之间的相互关系。此外，将通过与未感染艾滋病毒的人群研究合作，审查潜在的艾滋病毒特定代谢组发现。这项研究的结果将为更全面、更纵向地衡量代谢组学特征的更大规模的研究提案提供初步数据。这些研究将促进我们对HIV感染和心血管疾病发病机制的了解，并为有效预防和处理HIV感染患者的心血管疾病提供有用的信息。

 DESCRIPTION (provided by applicant): This K01 Career Development Award application proposes a multidisciplinary 4-year training program to provide the candidate, Dr. Qibin Qi, with the experience and resources necessary to launch a successful career as an independent investigator. The training plan, developed closely with primary mentor Dr. Kaplan Robert, co-mentor Dr. Kathryn Anastos, and an Advisory Committee, will broaden Dr. Qi's research experience and expertise, including metabolomics, biostatistics and HIV infection and cardiovascular disease (CVD) epidemiology. The proposed research project, building upon two well-characterized HIV cohorts (the Women's Interagency HIV Study [WIHS] and the Multicenter AIDS Cohort Study [MACS]), offers the candidate an outstanding opportunity to become proficient in the novel area of metabolomics research as well as in HIV infection and CVD epidemiology. Taking advantage of archived blood samples, extensive data on HIV-infection related factors, longitudinal measurements of carotid artery plaque, and genomic data in the WIHS and MACS, this project proposes to examine plasma levels of metabolites among 495 women and men, aged = 45 years old, without carotid artery plaque at baseline (338 HIV+ and 157 HIV- subjects; 103 subjects had incident carotid plaque over 7-year follow-up measured by B mode ultrasound). Associations of HIV infection and related factors with prior informed cardiometabolic-associated metabolites (e.g., branched-chain amino acids), and associations between these metabolites and progression of subclinical carotid atherosclerosis (incident carotid artery plaque) will be examined. In exploratory analyses, advance analytical approached (e.g., network analysis) will be applied to identify novel metabolomic signatures related to HIV infection and subclinical atherosclerosis progression, and to generate a network illustrating interrelationships between genes, metabolites, HIV infection and CVD. In addition, potential HIV-specific metabolomic findings will be examined through collaborations with HIV-uninfected population studies. Findings from this study will provide preliminary data for a larger study proposal to measure metabolomics profiling more comprehensively and longitudinally. These studies will advance our understanding of pathogenesis of HIV infection and CVD and provide useful information for effective strategies in the prevention and management of CVD in HIV-infected patients.