Development and role of coronary collaterals

The collateral circulation that develops in response to gradual and progressive coronary artery occlusion can maintain the structural and functional integrity of the subtended myocardium to an astonishing degree, provided the speed of the stenosing process is not too great. Collateral development occurs by recapitulation of ontogeny: patterns of morphogenic gene expression normally active only during embryonic development are recalled for vasculogenesis (large vessel formation, as in human and canine collaterals) and angiogenesis (capillary sprouting, as in human and porcine hearts). Vascular cell proliferation is induced by ischemia-related growth factor production. However, tissue growth alone is not enough for vasculogenesis (it would by itself cause lumen reduction). Remodeling, that is, the controlled destruction and complete reconstruction of the enlarged vessel, takes place involving the concerted action of proteases. For unknown reasons, the growth-remodeling process provides only ~50% of the blood-conducting capacity of the large vessel it has replaced. This leaves room for improvement by somatic gene therapy and by drugs to be developed.