Role of Hematopoietic System and Proteomics in HIV-Associated Cardiovascular Disease

造血系统和蛋白质组学在 HIV 相关心血管疾病中的作用

• 批准号: 10013759
• 负责人: Priscilla Y. Hsue
• 金额: $ 19.35万
• 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 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10013759
• 关键词: Anti-Inflammatory Agents; Atherosclerosis; Award; Basic Science; Biological; Blood Cells; Blood Vessels; Bone Marrow; Cardiac; Cardiology; Cardiovascular Diseases; Chronic; Clinic; Clinical; Clinical Data; Clinical Research; Clinical Trials; Coronary heart disease; Data; Development; Disease; Event; Extramedullary; Face; Foundations; Funding; General Population; Goals; Grant; HIV; HIV Infections; Heart failure; Hematopoiesis; Hematopoietic System; Hematopoietic stem cells; Image; Individual; Inflammation; Inflammatory; Infrastructure; Interleukin-1 beta; Intervention; Investigation; Kidney Diseases; Laboratories; Leadership; Link; Lipids; Malignant Neoplasms; Mentors; Meta-Analysis; Metabolic; Monoclonal Antibodies; Mutation; PET/CT scan; Pathogenesis; Pathway interactions; Persons; Play; Prevalence; Process; Proteins; Proteomics; Publications; Pulmonary Hypertension; Reporting; Research; Research Personnel; Resources; Risk; Risk Factors; Role; Sampling; San Francisco; Science; Site; Somatic Mutation; Technology; Time; Training; Translational Research; United States National Institutes of Health; Visit; Work; aged; aptamer; base; burden of illness; cardiovascular disorder risk; career; career development; clinical center; clinical predictors; comorbidity; disability-adjusted life years; fluorodeoxyglucose positron emission tomography; follow-up; hematopoietic tissue; immune activation; inflammatory marker; inhibitor/antagonist; lymph nodes; mortality; multidisciplinary; novel; patient oriented; patient oriented research; prevent; protein biomarkers; proteomic signature; stem cells; translational research program; translational study

Project Summary/Abstract 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 15 years studying cardiovascular disease (CVD) in the setting of HIV. The initial part of her career was spent 1) establishing a HIV Cardiology Clinic at Zuckerberg San Francisco General (ZSFG), 2) developing the infrastructure to perform patient oriented research in Cardiology including development of a vascular laboratory for clinical research, 3) performing studies that evaluate the mechanisms underlying HIV infection and CVD and 4); leading clinical trials aimed to reducing inflammation and CVD risk in HIV. The findings from her work have shown that 1) HIV infection is independently associated with CVD, independent of traditional risk factors or ART and 2) chronic inflammation in the setting of effectively treated HIV infection underlies this increased CV risk. Initial K24 support has led to a significant increase in the number of mentees, grants, and publications for Dr. Hsue and new research directions including use of novel imaging to assess HIV disease burden and identification of therapies to reduce HIV-associated inflammation and CV risk. For the K24 renewal period, her career goals are to perform cutting edge clinical/translational studies and mentoring that will lead to improvements in treating, identifying and preventing CVD among PLWH and also impact other comorbidities and HIV cure. Dr. Hsue plans to 1) expand her research to include the role of somatic mutations in the hematopoietic system (termed clonal hematopoiesis of indeterminate potential, CHIP) and proteomics in HIV-associated CVD; 2) continue her time spent mentoring junior investigators in the fields of HIV infection, inflammation, and CVD with a focus on transition to full-independence; 3) obtain leadership training to build clinical and translational research programs that can be used by mentees and will make her a better mentor. The majority of Dr. Hsue's career development will occur at UCSF which offers outstanding resources for clinical/translational research, basic science, imaging, HIV, and mentoring/leadership training. Her K24 proposal will extend upon her current NIH-funded investigations by studying the underlying mechanism of HIV- associated atherosclerosis in treated HIV with the following Specific Aims: Aim 1A: To determine if clonal hematopoiesis of indeterminate potential (CHIP) mutations are more prevalent in peripheral blood cells of PLWH vs. uninfected controls; Aim 1B: To determine whether the presence of CHIP mutations are associated with increased arterial inflammation and metabolic activity of the hematopoietic system as assessed by FDG- PET/CT; Aim 2A: To identify a unique proteomic signature in PLWH that is associated with arterial inflammation and metabolic activity of the hematopoietic system, and Aim 2B: to characterize changes in proteins and biological pathways that are altered after anti-inflammatory and lipid interventions. This proposal will provide subject visits, imaging, and clinical and laboratory data to support new investigators in clinical/ translational research in the field of HIV-related CVD and HIV disease pathogenesis including cure.

项目总结/文摘