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Cell-Type Specific Mechanisms of HIV Cardiomyopathy

HIV心肌病的细胞类型特异性机制

基本信息

批准号：
10534777
负责人：
Neil C Chi
金额：
$ 70.72万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-12-06 至 2025-11-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10534777
关键词：
Acute myocardial infarction Address Affect Age Years Arrhythmia Autopsy Behavior Biology Blood Cardiac Cardiac Myocytes Cardiomyopathies Cardiovascular Diseases Cardiovascular system Cell Communication Cell Nucleus Cells Cessation of life Chronic Clinical Collaborations Data Diagnostic Disease Disease model EFRAC Evaluation Expression Profiling Fibroblasts General Population Genetic Transcription Genomic approach Gifts Goals HIV HIV Infections HIV therapy HIV/AIDS Heart Heart Diseases Heart failure Homeostasis Human Immune Immune system In Vitro Incidence Inflammation Interdisciplinary Study Lead Lung Methods Modeling Molecular Myocardial Infarction Outcome Pathogenesis Pathologic Pathologic Processes Patients Persons Pilot Projects Population Process Research Research Personnel Risk Risk Factors Role San Francisco Science Sleep Stress Tissue Sample Tissues Translating antiretroviral therapy cardiovascular disorder risk cell behavior cell type cohort comorbidity coronary fibrosis gene regulatory network heart function high risk human pluripotent stem cell immune activation in vivo individualized medicine innovation insight interest interstitial novel programs response sudden cardiac death transcriptome sequencing

项目摘要

Project Summary By 2030, 73% of people with HIV will be ≥ 50 years of age and 78% will have cardiovascular disease. People with HIV have a 50% increased risk of acute myocardial infarction, a 61% higher risk of heart failure with reduced ejection fraction and > 4 fold higher rates of sudden cardiac death compared to the general population. In addition to traditional risk factors, HIV-associated features such as chronic inflammation and immune dysregulation in the setting of treated HIV infection are strong predictors of cardiovascular disease. However, studies elucidating the pathogenesis of heart failure in HIV have been largely descriptive and have thus provided limited insight into the underlying mechanisms of these disease processes. Thus, we propose to address the pathogenesis of heart failure in people with HIV through investigating the impact of HIV, immune activation and antiretroviral therapies on the broad range of cell types comprising the human heart. Overall, the proposed studies will illuminate underlying mechanisms of HIV cardiomyopathy, which may be translated to the creation of cell-type specific therapies for HIV-related cardiac diseases.

项目摘要到2030年，73%的艾滋病毒感染者将≥ 50岁，78%的人将患有心血管疾病。人感染艾滋病毒的人患急性心肌梗死的风险增加50%，患心力衰竭的风险增加61%，射血分数降低，心源性猝死发生率是一般情况的4倍以上人口除了传统的风险因素，艾滋病毒相关的特征，如慢性炎症和在接受治疗的HIV感染的情况下，免疫失调是心血管疾病的强有力的预测因子。然而，阐明HIV心力衰竭发病机制的研究主要是描述性的，因此对这些疾病过程的潜在机制提供了有限的了解。因此，我们建议通过研究艾滋病毒、免疫系统和心功能的影响，激活和抗逆转录病毒疗法对广泛的细胞类型，包括人类心脏。总的来说，这些研究将阐明HIV心肌病的潜在机制，为艾滋病毒相关心脏疾病创造细胞类型特异性疗法。