Regulation of the human coronary microcirculation

Atherosclerosis of conduit epicardial arteries is the principal culprit behind the complications of coronary heart disease, but a growing body of literature indicates that the coronary microcirculation also contributes substantially to the pathophysiology of cardiovascular disease. An understanding of mechanisms regulating microvascular function in humans is an essential foundation for understanding the role in disease, especially since these regulatory mechanisms vary substantially across species and vascular beds. In fact all subjects whose coronary tissue was used in the studies described have medical conditions that warrant cardiac surgery, thus relevance to the normal human must be inferential and is based on tissue from subjects without known arteriosclerotic disease. This review will focus on recent advances in the physiological and pathological mechanisms of coronary microcirculatory control, describing a robust plasticity in maintaining endothelial control over dilation, including mechanisms that are most relevant to the human heart. This article is part of a Special Issue entitled “Coronary Blood Flow”.

► Coronary blood flow is regulated by arterioles between 50–200 μm in diameter.
► Shear-induced dilation amplifies metabolic dilation by reducing upstream vascular resistance.
► Shear-induced endothelial hydrogen peroxide originates from mitochondria.
► This shear-released hydrogen peroxide dilates coronary arterioles from humans with CAD.
► Transient receptor potential vanilloid 4 channels are required for the dilation to shear.