Long-Term Endothelial Effects of COVID-19 in Obesity

COVID-19 对肥胖的长期内皮效应

基本信息

批准号：
10387464
负责人：
Naomi Miriam Hamburg
金额：
$ 73.11万
依托单位：
BETH ISRAEL DEACONESS MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-03-15 至 2026-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10387464
关键词：
2019-nCoV Acceleration Acute Adverse effects Age Aging Automobile Driving Autopsy Bioinformatics Biology of Aging Blood Vessels COVID-19 COVID-19 impact COVID-19 patient Cardiac Cardiovascular Physiology Cardiovascular system Case-Control Studies Cell Aging Cells Cessation of life Clinical Complement Coronary Coronavirus Critical Illness Cross-Sectional Studies Development Disease Disease susceptibility Elements Endothelial Cells Endothelium Enrollment Event Fibrin fragment D Foundations Future Gene Expression Gene Expression Profiling Heart Human Image Individual Inflammation Inflammatory Insulin Resistance Investigation Kidney Lead Link Longitudinal observational study Lung Medical center Metabolic dysfunction Metformin Microvascular Dysfunction Minority Molecular Nitric Oxide Non obese Obesity Obesity associated cardiovascular disease Oxidative Stress Participant Pathway interactions Patients Peripheral Phenotype Plasma Positioning Attribute Positron-Emission Tomography Preventive Production Prospective Studies Proteomics Race Recombinants Recovery Research Research Personnel SARS-CoV-2 infection SARS-CoV-2 infection history Severity of illness Symptoms Therapeutic Vascular Diseases Vascular Endothelium Venous Viral Visceral cardiovascular effects endothelial dysfunction ethnic difference ethnic minority population experience gene complementation high body mass index high risk population insight molecular phenotype multidisciplinary obese patients obese person persistent symptom post SARS-CoV-2 infection prospective public health relevance racial minority response senescence severe COVID-19 sex targeted treatment thrombotic vascular bed von Willebrand Factor

项目摘要

Project Summary/Abstract Coronavirus 2019 (COVID-19) has infected more than 29 million globally. While the majority of individuals experience mild symptoms, the presence of obesity among other factors identifies a particularly high-risk group of individuals for development of severe COVID-19. Severe COVID-19 is characterized by exuberant inflammation and vascular dysfunction, but long-term cardiovascular effects remain unclear. We hypothesize that COVID-19 infection has widespread and long-lasting deleterious effects on endothelial function, including molecular pathways of cellular senescence and inflammation among obese individuals. We propose to prospectively study 100 obese and non-obese individuals with history of COVID-19 infection and 50 age- and sex-matched controls. To gain further insights into underlying mechanisms of vascular dysfunction, we will pursue three related lines of investigation: In Aim 1, we will study the effect of COVID-19 across vascular beds including peripheral and coronary microvascular function. In Aim 2, we will investigate the association of COVID-19 and molecular pathways of endothelial activation and senescence using circulating proteomic profiling, gene expression profiling of freshly isolated human endothelial cells, complemented by interrogation of targeted endothelial pathways. In Aim 3, we will conduct a prospective longitudinal observational study to examine the effect of COVID-19 on trajectories of peripheral and coronary microvascular function and endothelial phenotype over the course of 6 months. This proposal leverages a unique and highly experienced multidisciplinary team of investigators with expertise in obesity-related cardiovascular disease, endothelial and aging biology, coronary microvascular dysfunction, and bioinformatics. Importantly, our investigative team has a track record of successfully enrolling minority participants across two medical centers. With a disproportionate burden of severe COVID-19 among racial and ethnic minority groups, we will be uniquely positioned to examine race/ethnic differences in exploratory analyses. These studies have the potential to provide important insights into mechanisms driving endothelial inflammation and cardiovascular consequences of COVID-19 among obese individuals and will lay the foundation for future studies focused on long-term cardiovascular complications and therapeutic strategies.

项目概要/摘要 2019 年冠状病毒 (COVID-19) 已感染全球超过 2900 万人。虽然大多数人出现轻微症状，肥胖等因素的存在确定了一个特别高风险的群体个人发展为严重 COVID-19 的情况。严重的 COVID-19 的特点是炎症和血管功能障碍，但长期心血管影响仍不清楚。我们假设 COVID-19 感染对内皮功能具有广泛且持久的有害影响，包括肥胖个体细胞衰老和炎症的分子途径。我们建议前瞻性研究了 100 名有 COVID-19 感染史的肥胖和非肥胖个体以及 50 名年龄和年龄性别匹配的对照。为了进一步了解血管功能障碍的潜在机制，我们将进行三个相关的研究方向：在目标 1 中，我们将研究 COVID-19 对血管床的影响包括外周和冠状动脉微血管功能。在目标 2 中，我们将调查使用循环蛋白质组学研究 COVID-19 以及内皮激活和衰老的分子途径新鲜分离的人内皮细胞的分析、基因表达分析，并辅以询问靶向内皮途径。在目标 3 中，我们将进行一项前瞻性纵向观察研究检查 COVID-19 对外周和冠状动脉微血管功能轨迹的影响， 6个月内的内皮表型。该提案利用了独特且经验丰富的多学科研究团队拥有肥胖相关心血管疾病、内皮和衰老生物学、冠状动脉微血管功能障碍和生物信息学。重要的是，我们的调查团队已经在两个医疗中心成功招募少数族裔参与者的记录。与一个由于严重的 COVID-19 在少数种族和族裔群体中造成的负担不成比例，我们将是独一无二的定位于在探索性分析中检查种族/民族差异。这些研究有潜力为驱动内皮炎症和心血管后果的机制提供重要见解肥胖个体中 COVID-19 的流行情况，并将为未来的长期研究奠定基础心血管并发症和治疗策略。