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Dynamic Role of Hyaluronan in Ventricular Remodeling

透明质酸在心室重构中的动态作用

基本信息

批准号：
10582530
负责人：
Danielle T Little
金额：
$ 3.46万
依托单位：
UNIVERSITY OF LOUISVILLE
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：
2022-02-01 至 2025-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10582530
关键词：
Acute Acute myocardial infarction Adenoviruses Advocate Atomic Force Microscopy Biomechanics Cardiac Cardiac Myocytes Cells Chronic Chronic Phase Cicatrix Collaborations Collagen Data Deposition Development Disease Echocardiography Elements Embryo Enterobacteria phage P1 Cre recombinase Environment Enzymes Event Extracellular Matrix Family Fellowship Fibroblasts Fibrosis Future Goals HAS2 gene Health Heart Heart failure Hour Hyaluronan Hyaluronidase Immune In Vitro Infarction Inflammatory Intervention Ischemia Knowledge Laboratory Research Lipids Literature Metabolism Molecular Weight Mus Muscle Cells Mutant Strains Mice Myocardial Infarction Myocardium Organ Pathology Phase Play Process Production Proliferating Proteins Regulation Research Role Rupture Scientist Shapes Techniques Therapeutic Tissues Training Translating Ventricular Ventricular Function Ventricular Remodeling acute wound cell type disorder risk gain of function heart function histological stains in vivo evaluation innovation insight loss of function novel novel therapeutic intervention prevent tool wound healing

项目摘要

Project Abstract The extracellular matrix (ECM) provides structural and functional support for the myocardium; however, heart failure alters the composition of the ECM. The ECM is composed of a number of proteins, lipids, and saccharides, yet their function is largely unknown. We found that one of the most abundant components of the ECM, hyaluronan (HA), accumulates following myocardial infarction; however, the role of HA following during infarct- induced heart failure is not known. Fibroblasts are a major cell type involved in ventricular remodeling. Once activated, fibroblasts proliferate and produce ECM components, such as collagen and HA. These events are associated with acute scar formation and chronic ventricular remodeling. In this project, I will explore the extent to which fibroblast-derived HA impacts the extracellular matrix. Specifically, I will study fibroblasts collagen secretion when HA metabolism is manipulated. Additionally, I will examine the extent to which fibroblast-derived HA contributes to acute scar formation post-MI. Finally, I will determine the extent to which fibroblast-derived hyaluronan contributes to chronic ventricular remodeling. We contend that acute increases in HA accumulation are required for scar formation following acute MI; however, the persistent, excessive production of HA provokes fibrosis beyond the initial scar. Hence, we predict that HA has a dynamic role following infarct-induced heart failure: beneficial early and maladaptive late. Taken together, these studies will provide novel insight into the role of HA in collagen secretion, acure scar formation, and chronic fibrosis. With this fundamental knowledge, we can, in future studies, explore therapeutic approaches. Regardless of the specific findings of this research plan, this fellowship will serve as an excellent vehicle to enhance my training so I can eventually become an independent scientist leading my own research laboratory. The combination of the experimental plan, experimental tools, my sponsor, the environment, advanced coursework, and professional development opportunities creates a high likelihood for me to realize my eventual goals and contribute significantly to the literature in the process.

项目摘要