Cardiomyocyte Proliferation and Ventricular Morphogenesis

描述（由申请人提供）：这项工作的主要目的是了解心脏心室腔形成的基础。该项目特别考虑了两个 不同的过程：心肌细胞（心肌细胞）如何在数量上扩大（增殖），以及冠状血管如何形成。这些过程是相互关联的，因为它们受到来自心脏外层（一种称为心外膜的细胞类型）的信号的控制。本项目旨在了解这些信号的作用和机制基础，主要利用基因工程小鼠，胚胎小鼠组织和组织培养细胞进行这项研究。 公共卫生相关性：心脏病是西方世界死亡的主要原因，并且是有害的，因为受损的成人心肌大多无法自我修复和再生。成功再生所需的两个关键过程包括心肌的生长和功能性血管供应的重建。人们普遍认为，基于胚胎心脏发育期间发生的正常过程的策略将为成功治疗成人心脏病提供最大的可能性。该项目的主要重点是解决心肌和冠状血管形成如何在胚胎中发生。

DESCRIPTION (provided by applicant): The broad objective of this work is to understand the basis of formation of the ventricular chamber of the heart. This project specifically considers two distinct processes: how do cardiac muscle cells (cardiomyocytes) expand in number (proliferate), and how do coronary blood vessels form. These processes are related by virtue of being controlled by signals from the outer layer of the heart, a cell type called the epicardium. This project seeks to understand the role and mechanistic basis of these signals, primarily utilizing genetically engineered mice, explanted embryonic mouse tissue, and tissue culture cells to conduct this research. PUBLIC HEALTH RELEVANCE: Heart disease is the leading cause of death in the Western world, and is pernicious because damaged adult heart muscle is mostly not able to repair itself and regenerate. Two critical processes that would be needed for successful regeneration include the growth of cardiac muscle and the reformation of a functional vascular supply. It is widely felt that strategies based on normal processes that occur during embryonic heart development will offer the greatest likelihood for successful treatment of adult heart disease. The primary focus of this project is to address how cardiac muscle and coronary vascular formation occur in the embryo.