Coronary microcirculation in myocardial ischemia: A genetic perspective

Coronary microvascular dysfunction (CMD) is a major contributor to ischemic heart disease (IHD), acting both independently and together with atherosclerosis. CMD encompasses structural and functional microcirculatory changes that result in dysregulated coronary blood flow. Structural abnormalities include microvascular remodeling, resulting in arteriolar and capillary narrowing, perivascular fibrosis and capillary rarefaction. Endothelial dysfunction and smooth muscle cell hyperactivity further impair microcirculation. Genetic factors may play a crucial role in the pathophysiology of CMD, mainly due to single nucleotide polymorphisms (SNPs) in genes that regulate coronary blood flow and microcirculation structural modifications. This manuscript aims to review the genetic determinants of CMD, with particular focus on ion channels, microRNAs (miRNAs), and proteins involved in the endothelial environment. The improving knowledge about genetic aspects of CMD opens the possibility to have new biomarkers, improving diagnosis and the development of targeted treatments in light of an even more patient-tailored approach.