Cardiovascular system store-operated Ca2+ entry in endothelial pathophysiology

Abstract

Vascular endothelial cells have recently been demonstrated to express the store-operated channel protein Orai, representing a potential key player in endothelial Ca2+ homeostasis. Orai channels appear to serve endothelial signaling in a concerted manner within a network of ion channels and transport systems that are all intimately linked to the function of cellular Ca2+ storage compartments such as TRPC signalplexes. Physiological transitions between endothelial phenotypes and functional states are associated with reorganization of this store-dependent endothelial Ca2+ signaling network, which is highly sensitive to metabolic disturbances and typically impaired in early stages of vascular pathologies. Recent gain in knowledge on the molecular basis of store-operated Ca2+ entry into endothelial cells has paved the way towards novel strategies for the prevention of endothelial dysfunction as well as for promotion and control of vascular repair and remodeling. This chapter will focus on the potential role of endothelial store-operated signaling mechanisms in the pathogenesis of vascular disorders and provide an overview on the molecular targets involved in pathologically relevant disturbances in endothelial Ca2+ signaling.