[Bone and Calcium Research Update 2015. Intracellular Ca2+ regulation in endothelial cells]

Endothelial cells regulates vascular tonus and exerts anti-atherosclerotic effects in response to external stimulation via Ca2+-dependent production of vasoactive substances such as NO. Agonists such as ATP hydrolyze membrane PIP2 and release soluble IP3 into the cell. IP3 then binds to the IP3 receptor and mobilizes Ca2+ from endoplasmic reticulum Ca2+ stores, followed by Ca2+ influxes from the extracellular space. Such store-operated Ca2+ entry comprises organization of a Ca2+ signal complex at the local subplasmalemmal domain involving TRPC4, caveolin1, and STIM1, a Ca2+ sensor protein for intracellular Ca2+ stores. Genetic deletion of any component of these three proteins can lead to depressed Ca2+ influxes and changes of endothelial function. Further elucidation of spatiotemporally organized endothelial Ca2+ signaling is critical for understanding pathophysiology of cardiovascular diseases.