In turn, ER stress plays a critical role in Ca2+ handling in VSMCs, implying that hyperinsulinemia and IR indirectly alter the expression and function of the proteins of the functional unit (CaV1.2, SERCA, RyRs, and BKCa), dysregulating intracellular Ca2+ handling and impairing vascular tone. This evidence concerns the gene CACNA1C and Hyperinsulinemia.