Role of innate immunity in HIV related vascular disease: biomarkers & mechanisms

先天免疫在 HIV 相关血管疾病中的作用：生物标志物

• 批准号: 9172489
• 负责人: Robert C Kaplan
• 金额: $ 64.37万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE, INC
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-15 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9172489
• 关键词: Acquired Immunodeficiency Syndrome; Adult; Anti-Retroviral Agents; Antigen Presentation; Apolipoproteins; Archives; Arteries; Atherosclerosis; Automobile Driving; Benchmarking; Binding Proteins; Biological Markers; CD14 gene; CD4 Positive T Lymphocytes; Cardiovascular Diseases; Caring; Carotid Arteries; Cell Count; Chronic; Clinical; Coagulation Process; Cohort Studies; Comorbidity; Complement 4b; Data; Dendritic Cells; Development; Disease Progression; FCGR3B gene; Flavoring; Galectin 3; Gene Expression; Gene Expression Profile; Genes; Glucose; HIV; HIV Infections; Health; Hepatitis C virus; Immune; Immune system; Infection; Inflammation; Intervention; Investigation; Joints; Knowledge; Lesion; Link; Lipids; Measures; Mediating; Messenger RNA; Natural Immunity; PPAR Pathway; Participant; Pathway interactions; Patients; Pharmaceutical Preparations; Population; RNA; RNA Sequences; Recording of previous events; Research; Research Project Grants; Risk; Risk Factors; Role; Scanning; Serum; Signal Pathway; Site; Smoking; Specimen; Stratification; Surface; Testing; Thromboplastin; Thrombosis; Transcript; Ultrasonography; United States National Institutes of Health; Ursidae Family; Vascular Diseases; Vascular remodeling; Visit; Woman; arginase; base; cardiovascular disorder prevention; cardiovascular disorder risk; chemokine; clinical application; clinically relevant; co-infection; cohort; complement C5b; cytokine; genome wide association study; genome-wide analysis; hemoglobin-haptoglobin receptor; human FRAP1 protein; improved; inflammatory marker; insight; intimal medial thickening; loss of function; mRNA Expression; macrophage; monocyte; novel; prospective; public health relevance; scavenger receptor; transcriptome sequencing

 DESCRIPTION (provided by applicant): Innate immune system activation is a recognized feature of chronic HIV infection that may contribute to HIV disease progression as well increasingly important non-classic HIV complications such as cardiovascular disease (CVD). This proposal will a) identify mechanisms linking innate immunity with CVD in the setting of chronic, treated HIV infection; b) develop novel serum biomarkers for monocyte/macrophage related inflammation and coagulation that may stratify CVD risk in the HIV-infected population; c) use global sequencing of RNAs (RNA-Seq) to define HIV- and CVD-associated gain and/or loss of function of specific signaling pathways by studying CD14++ and CD14+CD16+ monocyte subsets from well-characterized HIV+ and HIV- patient groups. Extensively characterized HIV infected and HIV uninfected enrollees from the WIHS and MACS NIH cohorts are brought to bear in this interdisciplinary, multi-site investigation. This project will thereby provide insight into the observed links of HIV infection and related comorbidities (e.g., HCV coinfection) with CVD risk, identifying the innate immune system as a novel and modifiable explanatory pathway. This is of high clinical relevance given the need for improved CVD risk stratification, as well as the feasibility of intervening on mechanisms mediated by monocyte/macrophage activity. ¿