Connecting the coronaries: How the coronary plexus develops and is functionalized

Abstract

The establishment of the coronary circulation is one of the final critical steps during heart development. Despite decades of research, our understanding of how the coronary vasculature develops and connects to the aorta remains limited. This review serves two specific purposes: it addresses recent advances in understanding the origin of the coronary endothelium, and it then focuses on the last crucial step of coronary vasculature development, the connection of the coronary plexus to the aorta. The chick and quail animal models have yielded most of the information for how these connections form, starting with a fine network of vessels that penetrate the aorta and coalesce to form two distinct ostia. Studies in mouse and rat confirm that at least some of these steps are conserved in mammals, but gaps still exist in our understanding of mammalian coronary ostia formation. The signaling cues necessary to guide the coronary plexus to the aorta are also incompletely understood. Hypoxia-inducible transcription factor-1 and its downstream targets are among the few identified genes that promote the formation of the coronary stems. Together, this review summarizes our current knowledge of coronary vascular formation and highlights the significant gaps that remain. In addition, it highlights some of the coronary artery anomalies known to affect human health, demonstrating that even seemingly subtle defects arising from incorrect coronary plexus formation can result in significant health crises.

Coronary Artery Development: Progenitor Cells and Differentiation Pathways

“…There is great interest in understanding the connection event between the developing coronary plexus and aorta (reviewed in 9). This event is interesting from a developmental biology standpoint because the vessel growth here is highly targeted, requiring anastomosis with the aorta, but at the same time, requiring avoidance of the adjacent pulmonary artery, which will ultimately carry deoxygenated blood.…”

“…The cell types involved in coronary arteriogenesis are present in the adult, leaving open the possibility that they could be reactivated to stimulate new arteries in the adult. In this review, we focus on the recent findings in coronary vessel development, which have built upon past work comprehensively reviewed elsewhere (6–9). The overarching future goal of research in this field is to transform information on coronary artery development into meaningful clinical treatments that can lower the incidence of CAD-induced mortality and morbidity.…”

Coronary stem development in wild‐type and Tbx1 null mouse hearts

“…However, the cellular and molecular mechanisms underlying formation of the coronary tree, and in particular those defining the sites of future coronary ostia, remain poorly understood. Hypoxia, innervation, neural crest cells, epicardially derived cells, and second heart field (SHF) derived myocardium have been suggested to be involved in this process, as have different growth factors and cytokines (Eralp et al, ; Tomanek et al, ; Théveniau‐Ruissy et al, ; Wikenheiser et al, ; Arima et al, ; Chen et al, ; Dyer et al, ; Ivins et al, ).…”

Associations between a Genetic Risk Score for Clinical CAD and Early Stage Lesions in the Coronary Artery and the Aorta

“…Recent studies of embryos and fetuses confirm that the development of the coronary arteries in humans is similar to other mammalian and avian species[25, 26]. Specifically, the ostia and stems of the coronary arteries appear to be formed by the growth of a vascular plexus into the aorta that originates from the mesenchymal-containing atrioventricular cushions over the interventricular groove.…”