Molecular Regulation of Coronary Vessel Development

冠状动脉发育是心脏功能形成过程中最关键的事件之一。冠状动脉系统的正确组装和构型对于发育中的心脏的持续生长以及婴儿和成人的心脏功能的维持至关重要。冠状动脉发育是一个独特的血管形成过程，在有冠状动脉的脊椎动物心脏(包括人类)中似乎是保守的。虽然有几个小组已经描述了冠状动脉的发展，许多已知的基因突变会扰乱冠状动脉的形成，但令人惊讶的是，人们对潜在的相关项目知之甚少，有三个核心专注于阐明调节冠状动脉系统适当分化和模式的细胞和分子机制。我们提议的研究将检验我们关于冠状动脉系统祖细胞招募的假设。我们拟议的研究将检验我们的假设，即冠状动脉系统祖细胞的招募，它们在心脏内和心脏内的运动，它们向血管内皮细胞和平滑肌细胞的分化，以及它们进入功能血管床的模式。我们的数据将提供对冠状动脉发育的基本机制的洞察，以及对对婴儿和成人心脏功能如此有害的异常血管形成和模式的理解。给出了这一过程与我们目标的关系。

Development of the coronary vessels is one of the most critical events in the formation of a functional heart. Proper assembly and patterning of the coronary system is essential for the continued growth of the developing heart and as well as maintenance of cardiac function in the infant and adult. Coronary development is a unique process of blood vessel formation, and appears to be conserved among vertebrate hearts (including human) with coronary vessels. While several groups have described coronary development and many genetic mutations are known to disrupt coronary vessel formation, surprisingly little is known about the underlying related projects and three cores focused on elucidating the cellular and molecular mechanisms that regulate the proper differentiation and patterning of the coronary system. Our proposed studies will test our hypothesis concerning the recruitment of progenitors to the coronary system. Our proposed studies will test our hypothesis concerning the recruitment of progenitors to the coronary system, their movement to and within the heart, their differentiation into vascular endothelial and smooth muscle cells and their patterning into a functional vascular bed. Our data will provide insight into the basic mechanisms governing coronary vessel development and an understanding of anomalous vessel formation and patterning that is so deleterious to the function of infant and adult hearts. The relationship of the process to our aims is given.