Ca signaling in vascular smooth muscle and endothelial cells in blood vessel remodeling: a review.

Vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) act together to regulate blood pressure and systemic blood flow by appropriately adjusting blood vessel diameter in response to biochemical or biomechanical stimuli. Ion channels that are expressed in these cells regulate membrane potential and cytosolic Ca concentration ([Ca]) in response to such stimuli. The subsets of these ion channels involved in Ca signaling often form molecular complexes with intracellular molecules via scaffolding proteins. This allows Ca signaling to be tightly controlled in localized areas within the cell, resulting in a balanced vascular tone. When hypertensive stimuli are applied to blood vessels for extended periods, gene expression in these vascular cells can change dramatically. For example, alteration in ion channel expression often induces electrical remodeling that produces a depolarization of the membrane potential and elevated [Ca]. Coupled with endothelial dysfunction blood vessels undergo functional remodeling characterized by enhanced vasoconstriction. In addition, pathological challenges to vascular cells can induce inflammatory gene products that may promote leukocyte infiltration, in part through Ca-dependent pathways. Macrophages accumulating in the vascular adventitia promote fibrosis through extracellular matrix turnover, and cause structural remodeling of blood vessels. This functional and structural remodeling often leads to chronic hypertension affecting not only blood vessels, but also multiple organs including the brain, kidneys, and heart, thus increasing the risk of severe cardiovascular events. In this review, we outline recent advances in multidisciplinary research concerning Ca signaling in VSMCs and ECs, with an emphasis on the mechanisms underlying functional and structural vascular remodeling.