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: 8846979
• 负责人: Robert C Kaplan
• 金额: $ 92万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 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/8846979
• 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 Association; Disease Progression; FCGR3B gene; Flavoring; Galectin 3; Gene Expression; Gene Expression Profile; Genes; Glucose; HIV; HIV Infections; 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; Thick; 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; cohort; complement C5b; cytokine; genome wide association study; hemoglobin-haptoglobin receptor; human FRAP1 protein; improved; inflammatory marker; insight; intima media; 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（由申请人提供）：先天免疫系统激活是慢性 HIV 感染的一个公认特征，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) 确定机制。在慢性、已治疗的 HIV 感染中将先天免疫与 CVD 联系起来；b) 开发单核细胞/巨噬细胞相关炎症和凝血的新型血清生物标志物，可以对 HIV 感染人群的 CVD 风险进行分层；通过研究来自明确的 HIV+ 和 HIV- 患者群体的 CD14++ 和 CD14+CD16+ 单核细胞亚群，使用 RNA 全局测序 (RNA-Seq) 来定义与 HIV 和 CVD 相关的特定信号通路功能的获得和/或丧失。来自 WIHS 和 MACS NIH 队列的 HIV 感染者和未感染者参与了这项跨学科、多地点的调查，从而深入了解观察到的 HIV 感染之间的联系。以及与 CVD 风险相关的合并症（例如 HCV 合并感染），将先天免疫系统确定为一种新颖且可修改的解释途径，考虑到改进 CVD 风险分层的需要以及干预机制的可行性，这具有很高的临床相关性。由单核细胞/巨噬细胞活性介导。