HIV Infection, Metabolites and Subclinical Atherosclerosis

 描述（由申请人提供）：此K 01职业发展奖申请提出了一个多学科的4年培训计划，为候选人Qibin Qi博士提供作为独立研究者成功开展职业生涯所需的经验和资源。该培训计划与主要导师Kaplan Robert博士、共同导师Kathryn Anavalet博士和咨询委员会密切合作，将扩大Qi博士的研究经验和专业知识，包括代谢组学、生物统计学和艾滋病毒感染和心血管疾病（CVD）流行病学。拟议的研究项目，建立在两个良好的特点艾滋病毒队列（妇女的机构间艾滋病毒研究[WIHS]和多中心艾滋病队列研究[MACS]），为候选人提供了一个出色的机会，成为精通代谢组学研究的新领域，以及在艾滋病毒感染和心血管疾病流行病学。利用存档的血液样本、关于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中的基因组数据，本项目建议检查495名年龄≥ 45岁、基线时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名受试者在7年随访期间通过B模式超声测量发生颈动脉斑块）。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），以及这些代谢物与亚临床颈动脉粥样硬化（偶发颈动脉斑块）进展之间的关联。在探索性分析中，先进的分析方法（例如，网络分析）将被应用于鉴定与HIV感染和亚临床动脉粥样硬化进展相关的新的代谢组学特征，并生成说明基因、代谢物、HIV感染和CVD之间的相互关系的网络。此外，将通过与未感染艾滋病毒的人群研究合作来检查潜在的艾滋病毒特异性代谢组学发现。这项研究的结果将为更大规模的研究提案提供初步数据，以更全面和纵向地测量代谢组学分析。这些研究将促进我们对HIV感染和CVD发病机制的理解，并为HIV感染患者CVD的预防和管理提供有用的信息。

 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.