Long-Term Endothelial Effects of COVID-19 in Obesity

项目总结/摘要 2019冠状病毒（COVID-19）已感染全球超过2900万人。虽然大多数人 经历轻微的症状，肥胖等因素的存在确定了一个特别高的风险群体 个人发展为严重的COVID-19。严重的COVID-19的特点是旺盛的 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和持久的有害影响，包括 肥胖个体中细胞衰老和炎症的分子途径。我们建议 前瞻性研究100名有COVID-19感染史的肥胖和非肥胖个体， 性别匹配的对照组。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：在目标1中，我们将研究COVID-19对血管床的影响 包括外周和冠状微血管功能。在目标2中，我们将研究 使用循环蛋白质组学研究COVID-19和内皮激活和衰老的分子途径 分析，新鲜分离的人内皮细胞的基因表达谱，辅以询问 靶向内皮细胞通路。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， 内皮细胞表型。该提案利用了一个独特的和经验丰富的 一个多学科的研究团队，在肥胖相关的心血管疾病，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，我们的调查小组 在两个医疗中心成功招募少数民族参与者的记录。与 种族和少数民族群体中严重的COVID-19负担不成比例，我们将是独一无二的 定位为在探索性分析中检查人种/种族差异。这些研究有可能 为驱动内皮炎症和心血管后果的机制提供重要见解 肥胖人群中COVID-19的发病率，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。

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.