Molecular Regulation of Coronary Vessel Development

冠状动脉血管的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模式对于心脏发育的持续生长以及婴儿和成人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，似乎在具有冠状血管的脊椎动物（包括人类）心脏中是保守的。虽然有几个研究小组已经描述了冠状动脉的发育，并且已知许多基因突变会破坏冠状动脉的形成，但令人惊讶的是，人们对潜在的相关项目知之甚少，并且有三个核心集中在阐明调节冠状动脉系统正确分化和模式的细胞和分子机制。我们提出的研究将检验我们关于冠状动脉系统祖细胞募集的假设。我们提出的研究将验证我们关于祖细胞向冠状动脉系统募集、向心脏和心脏内部移动、分化为血管内皮细胞和平滑肌细胞以及形成功能性血管床的假设。我们的数据将提供对控制冠状血管发育的基本机制的见解，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的目标之间的关系。

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.