Cardiovascular and hemostatic disorders: Role of STIM and orai proteins in vascular Disorders

Store-operated Ca²⁺ entry (SOCE) mediated by STIM and Orai proteins is a highly regulated and ubiquitous signaling pathway that plays an important role in various cellular and physiological functions. Endoplasmic reticulum (ER) serves as the major site for intracellular Ca²⁺ storage. Stromal Interaction Molecule 1/2 (STIM1/2) sense decrease in ER Ca²⁺ levels and transmits the message to plasma membrane Ca²⁺ channels constituted by Orai family members (Orai1/2/3) resulting in Ca²⁺ influx into the cells. This increase in cytosolic Ca²⁺ in turn activates a variety of signaling cascades to regulate a plethora of cellular functions. Evidence from the literature suggests that SOCE dysregulation is associated with several pathophysiologies, including vascular disorders. Interestingly, recent studies have suggested that STIM proteins may also regulate vascular functions independent of their contribution to SOCE. In this updated book chapter, we will focus on the physiological role of STIM and Orai proteins in the vasculature (endothelial cells and vascular smooth muscle cells). We will further retrospect the literature implicating a critical role for these proteins in vascular disease.