STIM1 and Orai1: Novel targets for vascular diseases?

The past five years have witnessed the discovery of the endoplasmic reticulum calcium (Ca ²⁺) sensor STIM1 and the plasma membrane Ca ²⁺ channel Orai1 as the bona fide molecular components of the store-operated Ca ²⁺ entry (SOCE) and the Ca ²⁺ release-activated Ca ²⁺ current (I _CRAC). It has been known for two decades that SOCE and I _CRAC are required for lymphocyte activation as evidenced by severe immunodeficient phenotypes in patients lacking I _CRAC. In recent years however, studies have uncovered expression of STIM1 and Orai1 proteins in various tissues and described additional roles for these proteins in physiological functions and pathophysiological conditions. Here, we will summarize novel findings pertaining to the role of STIM1 and Orai1 in the vascular system and discuss their potential use as targets in the therapy of vascular disease.