Cardiac Lymphatics in Development and Repair

心脏淋巴管的发育和修复

• 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
• 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

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起着重要作用 在整个身体。通过手术或其他方式破坏淋巴管功能， 放疗/化疗或器官损伤导致病理性水肿和随后的 间质纤维沉积和炎症。心脏含有密集的淋巴网络 与心肌的每次收缩表现出协调流动的血管。最近的研究， 包括我们自己的，已经揭示了心脏修复中心脏血管的关键作用， 维持急性心肌水肿后的心脏功能。几个开创性的 研究还表明，心脏动脉粥样硬化产生于至少4种不同的祖细胞， 细胞群，从而说明其独特的和多效性的调节过程中的发展 以及重塑和修复的条件。我们还发现， 与年龄匹配的雄性小鼠相比， 是女性某些形式心脏保护的基础。因此，总体目标是 这项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 在不同的发育和修复阶段。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髓质素肽的心脏保护功能的兴趣，我们认为， 我们处于独特的有利地位，可以解决几个有趣的假设。源自我们的 研究将提供概念上的新见解，在很大程度上未探索的作用，心脏 淋巴管在心脏发育、损伤和性别依赖性心脏保护中的作用。