Cardiac Lymphatics in Heart Failure

 描述（由申请人提供）：淋巴管在维持整个身体的间质液平衡方面发挥重要作用。它们还充当免疫细胞运输和成熟的管道。手术、放疗/化疗或器官损伤对淋巴管的功能性破坏导致病理性水肿和随后的间质纤维沉积和炎症。心脏包含密集的淋巴管网络，其随着心肌的每次收缩而表现出协调的流动。然而，淋巴功能障碍是否有助于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和遗传小鼠模型工具，以解决心脏疾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，可以分别解决心脏水肿增加或淋巴功能不全对心肌水肿消退或加重的影响。从我们的研究结果将提供概念新颖的见解，在很大程度上未探索的作用，心脏淋巴管在心肌水肿。

 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.