Cardiac Lymphatics in Development and Repair

心脏淋巴管的发育和修复

基本信息

批准号：
10190998
负责人：
Kathleen M Caron
金额：
$ 58.31万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-04-01 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10190998
关键词：
Acute Address Adult Age Anatomy Animal Model Arrestins Biochemical Biological Models Biological Process Biology Blood Vessels Cardiac Cardiac health Cardiovascular system Cell Surface Proteins Cells Characteristics Chemotherapy and/or radiation Chronic Clinical Clinical Trials Cues Data Databases Deposition Development Disease Edema Embryo Embryonic Development Exhibits Female Fibrosis Fluid Balance Foundations G-Protein-Coupled Receptors Genes Genetic Genetic Engineering Genetically Engineered Mouse Goals Grant Growth Heart Heterogeneity Inflammation Injury Intercellular Fluid Knowledge Laboratories Lead Ligands Liquid substance Lymphatic Lymphatic Diseases Lymphatic System Lymphatic function Lymphedema Maintenance Maps Molecular Mus Myocardial Myocardial Infarction Myocardium Operative Surgical Procedures Organ Outcome Pathogenesis Pathologic Pathway interactions Peptides Permeability Pharmacology Phenotype Plasma Population Population Genetics Positioning Attribute Pregnancy Prevalence Progress Reports Proteins Publishing Pulmonary Hypertension RAMP2 Regulation Reporter Research Proposals Resolution Role Septic Shock Signal Pathway Signal Transduction Signaling Protein Source Stress System Testing Time Tissues Transactivation Variant Vascular Endothelial Growth Factor Receptor-3 Ventricular Woman Work adrenomedullin base cadherin 5 cardiac repair cardiogenesis cardioprotection density diagnostic biomarker dosage genetic resource heart dimension/size heart function heart preservation insight interest interstitial lymphatic development lymphatic vessel male mouse model novel prognostic repaired sex stem cells therapeutic target tool

项目摘要

Project Abstract Lymphatic vessels serve an essential function in maintaining interstitial fluid balance throughout the body. Functional disruption of lymphatic vessels by either surgery, radiation/chemotherapy or organ damage results in pathological lymphedema and subsequent interstitial fibrous deposition and inflammation. The heart contains a dense network of lymphatic vessels that exhibit coordinated flow with each contraction of the myocardium. Recent studies, including our own, have revealed a critical role for cardiac lymphatics in cardiac repair and maintenance of cardiac function following acute myocardial edema. Several groundbreaking studies have furthermore shown that cardiac lymphatics arise from at least 4 different progenitor cell populations, thereby illustrating their distinct and pleiotropic regulation during development and conditions of remodeling and repair. We have also discovered a significant increase in the number of cardiac lymphatics of female mice, compared to age-matched male mice, which could be the basis underlying some forms of cardioprotection in women. Therefore, the overall goal of this research proposal is to develop sophisticated cell based systems and genetic mouse model tools to address the function and modulation of cardiac lymphatic vessels in males and females and during different stages of development and repair. Based on our expertise in lymphatic vessel biology and our interest in the cardioprotective functions of adrenomedullin peptide, we feel that we are uniquely well-positioned to address several intriguing hypotheses. Results from our studies will provide conceptually novel insights into the largely unexplored role of cardiac lymphatic vessels in heart development, injury and sex-dependent cardioprotection.

项目摘要淋巴管在维持间质流体平衡方面起着重要的作用整个身体。两项手术的功能破坏淋巴管，辐射/化学疗法或器官损伤导致病理淋巴水肿，随后导致间质纤维沉积和炎症。心脏含有密集的淋巴网络表现出与心肌每次收缩的协调流动的血管。最近的研究，包括我们自己的包括心脏淋巴管在心脏修复和急性心肌水肿后心脏功能维持。几个开创性研究还表明，心脏淋巴管至少由4个不同的祖细胞产生细胞种群，从而说明了它们在发育过程中的独特和多效调节以及重塑和修复的条件。我们还发现了与年龄匹配的雄性小鼠相比，雌性小鼠的心脏淋巴管数量成为女性中某些形式的心脏保护的基础。因此，总体目标该研究建议是开发基于复杂的细胞系统和遗传小鼠模型解决男性和女性心脏淋巴管功能和调制的工具以及在开发和维修的不同阶段。基于我们在淋巴管方面的专业知识生物学和我们对肾上腺甲素肽的心脏保护功能的兴趣，我们感到我们的位置很独特，可以解决一些有趣的假设。我们的结果研究将在概念上提供新的见解，以了解心脏的很大程度上未开发的作用心脏发育，损伤和性依赖性心脏保护的淋巴管。