Cardiac Lymphatics in Development and Repair

项目摘要 淋巴管在维持组织间液体平衡中起着至关重要的作用 遍及全身。两种手术中的任一种都会造成淋巴管功能障碍， 放射/化疗或器官损害导致病理性淋巴水肿和随后的 间质纤维沉积和炎症。心脏含有致密的淋巴管网络。 随着心肌的每次收缩而表现出协调流动的血管。最近的研究表明， 包括我们自己在内，已经揭示了心脏淋巴管在心脏修复和修复中的关键作用 急性心肌水肿后心功能的维持。几项开创性的工作 研究进一步表明，心脏淋巴管至少来自4种不同的祖细胞。 细胞群体，从而说明它们在发育过程中的不同和多效性调节 以及改建和修复的条件。我们还发现，在全球范围内 雌性小鼠的心脏淋巴管数量，与年龄匹配的雄性小鼠相比，这可以 是女性某些形式心脏保护的基础。因此，总的目标是 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 研究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 生物学和我们对肾上腺髓质素多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，可以解决几个耐人寻味的假设。结果来自我们的 研究将为心脏在很大程度上尚未探索的作用提供概念上的新见解 淋巴管在心脏发育、损伤和性别依赖性心脏保护中的作用。

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.