Cardiac Lymphatics in Heart Failure

心力衰竭中的心脏淋巴管

• 批准号: 9417070
• 负责人: Kathleen M Caron
• 金额: $ 37.5万
• 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 2020-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9417070
• 关键词: Acute; Address; Adult; Anatomy; Animals; Area; Biological Process; Biology; Blood Vessels; Cardiac; Cardiac Edema; Cardiac health; Cardiovascular system; Cell physiology; Cells; Chronic; Clinic; Clinical; Clinical Trials; Connexin 43; Coupling; Data; Deposition; Disease; Edema; Embryo; Embryonic Development; Exhibits; Fibrosis; Fluid Balance; Functional disorder; G-Protein-Coupled Receptors; Gap Junctions; Genes; Genetic; Genetically Engineered Mouse; Goals; Grant; Health; Heart; Heart Diseases; Heart Injuries; Heart failure; Immune; Infarction; Inflammation; Injury; Intercellular Fluid; Ischemia; Japan; Knowledge; Laboratories; Lead; Liquid substance; Lung; Lymphangiogenesis; Lymphatic; Lymphatic Capillaries; Lymphatic vessel; Lymphedema; Maintenance; Measures; Mediating; Methods; Modeling; Molecular; Mus; Myocardial; Myocardial Infarction; Myocardial Ischemia; Myocardium; Natural Immunity; Operative Surgical Procedures; Organ; Outcome Study; Pathogenesis; Pathologic; Pathway interactions; Peptides; Peripheral; Pharmacology; Phenotype; Plasma; Positioning Attribute; Pregnancy; Prevalence; Prognostic Marker; Proteins; Pulmonary Hypertension; Radiation; Research; Research Proposals; Resolution; Role; Shock; Stains; Stress; Surgical Models; System; Tissues; Translating; United States National Institutes of Health; Vascular System; Venous Pressure level; Ventricular; Ventricular Function; adrenomedullin; base; cardiogenesis; cardioprotection; chemotherapy; clinically relevant; diagnostic biomarker; heart function; improved; insight; interest; interstitial; loss of function; mouse model; novel; public health relevance; septic; tool; trafficking; urinary

 DESCRIPTION (provided by applicant): Lymphatic vessels serve an essential function in maintaining interstitial fluid balance throughout the body. They also serve as a conduit for the trafficking and maturation of immune cells. 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. However, whether lymphatic dysfunction contributes to the pathophysiological progression of heart injury following myocardial ischemia remains unknown. Furthermore, we lack a full understanding of the consequences of myocardial edema on heart function following ischemic heart disease. Therefore the overall goal of this research proposal is to develop sophisticated surgical and genetic mouse model tools to address the function and modulation of cardiac lymphatic vessels in heart disease. 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 the effects of either increased cardiac lymphatics or lymphatic insufficiency on the resolution or exacerbation of myocardial edema, respectively. Results from our studies will provide conceptually novel insights into the largely unexplored role of cardiac lymphatic vessels in myocardial edema.

 描述（由申请人提供）：淋巴管在维持全身间质液平衡方面发挥着重要作用，它们还充当通过手术、放疗/化疗或免疫细胞功能性破坏的管道。器官损伤导致病理性淋巴水肿以及随后的间质纤维沉积和炎症心脏含有密集的淋巴管网络，其与心肌的每次收缩表现出协调的流动。淋巴功能障碍导致心肌缺血后心脏损伤的病理生理进展仍不清楚。此外，我们对缺血性心脏病后心肌水肿对心脏功能的影响缺乏充分的了解，因此本研究提案的总体目标是开发复杂的外科手术。和遗传小鼠模型工具来解决心脏病中心脏淋巴管的功能和调节。基于我们在淋巴管生物学方面的专业知识以及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，可以分别解决心脏淋巴管增加或淋巴管不足对心肌水肿消退或恶化的影响，我们的研究结果将为心脏淋巴管在心肌中尚未探索的作用提供概念上的新颖见解。浮肿。