Transient Receptor Potential Channels in Metabolic Syndrome-Induced Coronary Artery Disease

Abstract

Cardiovascular disease is the leading cause of death in the developed world. Coronary artery disease (CAD) is greatly exacerbated by underlying metabolic syndrome, which is defined as the presence of three or more of the following cardiovascular risk factors: obesity, glucose intolerance, insulin resistance, dyslipidemia, and hypertension. Alterations in the endothelial lining of the vascular wall and smooth muscle phenotype are key components in the underlying pathology. Both endothelial dysfunction and smooth muscle cell phenotype switching are mediated, at least in part, by altered intracellular Ca2+ handling. Transient receptor potential (TRP) channels have been implicated in CAD progression, both in endothelial dysfunction and smooth muscle phenotypic changes. Despite the widespread distribution of TRP channels in numerous cell types and the involvement in many diseases, there is a relative paucity of data on the role of TRP channels in CAD. TRP canonical (TRPC) channels are located on coronary smooth muscle (CSM) cell membranes and are involved in mediating Ca2+ entry. Increases in CSM TRPC expression and function are associated with CAD progression. In contrast, TRP vanilloid (TRPV) receptors are located primarily on the coronary endothelium, and function in normal physiology to increase intracellular Ca2+ in response to ligands or sheer stress, leading to endothelial-dependent vasodilation. Decreases in endothelial TRPV receptors function and expression are associated with progression of CAD. The loss of proper balance between CSM TRPC and endothelial TRPV contributes, at least in part, to CAD progression.