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. ¿

 描述（由适用提供）：先天免疫系统激活是慢性HIV感染的公认特征，可能导致HIV疾病进展以及日益重要的非经典HIV并发症，例如心血管疾病（CVD）。该提案将a）在慢性治疗的HIV感染的情况下确定将先天免疫组织化学与CVD联系起来的机制； b）开发用于单核细胞/巨噬细胞相关的炎症和凝结的新型血清生物标志物，这些炎症可能会使HIV感染人群中的CVD风险分层； c）使用RNA（RNA-SEQ）的全局测序来定义与特定信号传导途径的HIV和CVD相关的增益和/或通过研究CD14 ++和CD14+ CD16+单核细胞亚群的特定信号通路功能的丧失，从良好的HIV HIV HIV+和HIV- HIV-患者组中。在这项跨学科的多站点投资中，将受到WIHS和MACS NIH队列的艾滋病毒感染和未感染的HIV未感染的艾滋病毒的特征。因此，该项目将洞悉与CVD风险相关的HIV感染和相关合并症（例如HCV共感染）的联系，从而将先天免疫系统确定为一种新颖且可修改的利用途径。鉴于需要改善CVD风险分层，以及介入由单核细胞/巨噬细胞活性介导的机制的可行性，这具有很高的临床相关性。 »