Cardiac Lymphatics in Development and Repair

心脏淋巴管的发育和修复

基本信息

批准号：
10630198
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/10630198
关键词：
Acute Address Age Anatomy Animal Model Biochemical Biological Models Biological Process Biology Blood Vessels Cardiac Cardiac health Cardiovascular system Cell Surface Proteins Cells Characteristics Chronic Clinic Clinical Clinical Trials Cues Data Databases Deposition Development Disease Edema Embryo Embryonic Development Exhibits Female Fibrosis Fluid Balance G-Protein-Coupled Receptors Genes Genetic Genetic Engineering Genetically Engineered Mouse Goals Grant Growth Heart Heterogeneity Human Inflammation Injury Intercellular Fluid Japan Knowledge Laboratories Ligands Liquid substance Lymphangiogenesis Lymphatic Lymphatic Diseases Lymphatic System Lymphatic function Lymphedema Maintenance Maps Molecular Mus Myocardial Myocardial Infarction Myocardium Natural Immunity Operative Surgical Procedures Organ Outcome Pathogenesis Pathologic Pathway interactions Peptides Permeability Phenotype Plasma Population Population Genetics Positioning Attribute Pregnancy Prevalence Progress Reports Proteins Publishing Pulmonary Hypertension RAMP2 Radiation 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 Ventricular Function Woman Work adrenomedullin beta-arrestin cadherin 5 cardiac repair cardiogenesis cardioprotection chemotherapy density diagnostic biomarker dosage genetic resource heart dimension/size heart function heart preservation improved insight interest interstitial lymphatic development lymphatic vessel male mature animal mouse model novel pharmacologic prognostic repaired sex stem cells therapeutic target tool vascular bed

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液平衡中发挥着重要作用遍布全身。通过手术破坏淋巴管的功能，放疗/化疗或器官损伤导致病理性淋巴水肿和随后的间质纤维沉积和炎症。心脏含有密集的淋巴网络与心肌每次收缩表现出协调流动的血管。最近的研究，包括我们自己在内，已经揭示了心脏淋巴管在心脏修复和急性心肌水肿后维持心脏功能。多项突破性研究进一步表明，心脏淋巴管起源于至少 4 种不同的祖细胞细胞群，从而说明它们在发育过程中的独特和多效性调节以及改造和维修的条件。我们还发现显着增加与年龄匹配的雄性小鼠相比，雌性小鼠的心脏淋巴管数量，这可以是女性某些形式心脏保护的基础。因此，总体目标是该研究计划是开发复杂的基于细胞的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节的工具以及在发育和修复的不同阶段。基于我们在淋巴管方面的专业知识生物学以及我们对肾上腺髓质肽的心脏保护功能的兴趣，我们认为我们处于独特的有利位置来解决几个有趣的假设。我们的结果研究将为心脏的很大程度上未被探索的作用提供概念上新颖的见解淋巴管在心脏发育、损伤和性别依赖性心脏保护中的作用。