Vitamin D: evidence for an association with coronary collateral circulation development?

Contrary to past beliefs that the human coronary artery system lacks arterial anastomoses, it is now well established that coronary arteries possess a complex network of collateral circulation. Indeed, humans present one of the most developed coronary collateral systems amongst mammals [1]. Coronary collateral vessels originate during embryogenesis by a mechanism known as vasculogenesis, in which local signals promote the migration and differentiation of endothelial progenitor cells, resulting in de novo synthesis of blood vessels. After the embryological stage, development of collaterals relies on two other processes, namely angiogenesis and arteriogenesis. In angiogenesis, new capillaries are formed by sprouting of endothelial cells from pre-existing mature vessels under conditions of ischemia in response to several growth factors, including the vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). Vascular smooth muscle cells and pericytes also play a role in this process, being particularly important for the stabilization and maturation of new vessels. In contrast, arteriogenesis is defined as a structural remodelling of collaterals pre-formed during embryogenesis, promoted by a redistribution of blood flow and increased shear forces in vessel walls. This is especially observed after coronary total occlusion, when a decrease in pressure distal to the site of obstruction redirects the flow to arteries outside the ischemic area, leading to a positive remodelling of pre-existing arterioles, which can increase up to twelve fold in size [2].
Although functioning collaterals are observed in approximately 20% to 25% of individuals without coronary artery disease (CAD), the degree of coronary obstruction is one of the main determinants of collateralization – individuals with CAD present high prevalence of collaterals. In fact, collateral functionality has been associated with the severity of CAD, as it has been shown that patients with chronic total coronary occlusion have a higher collateral flow index (CFI) than those without chronic occlusion [3]. Therefore, collateral circulation seems to play an important role in salvaging areas of myocardium under ischemia, as exemplified by the observation that well-developed collaterals can limit infarct size [4]. In terms of prognostic value, Seiler et al. [5] evaluated the impact of collateral function, as assessed quantitatively by CFI, on all-cause mortality in a cohort of...


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