Development of the Coronary Vessel System

Abstract

Abstract-Formation of the coronary vessels is a fundamental event in heart development. Congenital abnormalities in the coronary system can have major deleterious effects on heart function. It is also possible that subtle variation in the patterning of coronary vessels has significant but uncharacterized effects on myocardial structure and function. In addition, generation of the coronary vascular system represents a complex system for analysis of regulation of cell fate determination, cell and epithelial migration, epithelial/mesenchymal transition, and patterning of a complex threedimensional structure. In this review, we present the descriptive embryology of this process as well as the recent data that shed light on the unique developmental mechanisms underlying generation of coronary vessels. This review also attempts to identify areas where additional research is needed and highlights the questions that must be answered for a meaningful understanding of coronary vessel development. Key Words: coronary vessels Ⅲ development P roblems of the coronary vascular system lead to major problems with the heart. Although the basic pathways taken by major coronary vessels over the surface of the heart are presented in cardiology textbooks, there is much variation in the pattern that is not well understood. Also, the enormity of the coronary system is not well appreciated as all, or nearly all, cardiac myocytes in mammalian hearts are in contact with a capillary and that the mammalian heart is one of the most vascularized organs of the body. Still, not a single cell that makes up the coronary system of the heart arises from the heart. Indeed, all the cells that make up the coronary system come from outside the heart are brought to the heart and differentiate into blood vessels only when they are in the heart. Indeed, all of this happens without ever tapping into the blood that courses through the heart lumen. The development and patterning of the coronary vascular system is a relatively unexplored area of vertebrate embryology that has important implications for human health.

Angiopoietin 1 expression levels in the myocardium direct coronary vessel development

“…The genesis of coronary vessels is an intricate process integrally associated with the development of the epicardium, a structure arising from the proepicardium, a derivative of the developing liver (Bernanke and Velkey, 2002;Reese et al, 2002). Our finding of a lack of coronary vessels appears to arise from problems with the proper formation and maintenance of the epicardium, similar to the ␣4 integrin (Yang et al, 1995), VCAM (Kwee et al, 1995), and WT1 (Moore et al, 1999) null mice.…”

“…The lack of coronary vasculature may reflect one of two things: (1) a defect with the epithelial-to-mesenchymal transition from the epicardium (Tevosian et al, 2000); or (2) a defect in the epicardium itself (Moore et al, 1999;Bernanke and Velkey, 2002;Morabito et al, 2002;Reese et al, 2002). Analysis of tissues for the presence or absence of the epicardium using the marker, Wilm's tumour 1 (WT1; Moore et al, 1999;Tevosian et al, 2000;Wagner et al, 2002) revealed that, in animals with no coronary vessels, the epicardium was either absent or defective.…”

“…Morphometric events such as looping, further septation, trabeculation, and thickening of the ventricular walls, and the shift of the atria to their adult positions then leads to the four compartments characteristic of the adult heart. Once the heart attains a certain size, nutrients and oxygen are no longer capable of diffusing from the blood to all of the surrounding tissues, and the heart generates its own vascular network called the coronary vessels (Bernanke and Velkey, 2002;Morabito et al, 2002;Reese et al, 2002).…”

“…Coronary vessel development is complex and involves the migration of proepicardial cells from the septum transversum onto the myocardial surface toward the atria and sinus venosus on one side, and toward the outflow tract on the other, forming the epicardium (Bernanke and Velkey, 2002;Reese et al, 2002). A subpopulation of these epicardial cells undergoes an epithelial-to-mesenchymal transition invading the subepicardial space, providing the smooth muscle cells of the coronary vasculature (Bernanke and Velkey, 2002;Reese et al, 2002).…”

“…A subpopulation of these epicardial cells undergoes an epithelial-to-mesenchymal transition invading the subepicardial space, providing the smooth muscle cells of the coronary vasculature (Bernanke and Velkey, 2002;Reese et al, 2002). Simultaneously, new blood capillaries form from the migrating angioblasts by means of vasculogenesis and recruit the epicardial-derived smooth muscle cells for structural support.…”