Journal of Endocrinology

Model for the role of smooth muscle cell-mineralocorticoid receptor (SMC-MR) in vascular function. At the cellular level, SMC-MR contributes to vascular tone and vasoconstriction, specifically in aging SMC. MR expression rises with age, resulting in suppressed transcription of miR-155, leading to the upregulation of the AngII type 1 receptor (AT1R) and l-type calcium channel (LTCC) subunit Cav1.2. SMC-MR contributes to vascular remodeling via several mechanisms, including:(1) Rho-kinase signaling, which is activated by aldosterone (Aldo) via SMC-MR or AngII, leading to c-src and Rho-associated kinase activation and SMC migration; (2) Placental growth factor (PlGF) signaling leading to vascular remodeling specifically in areas on vascular damage/injury, where the vascular endothelial growth factor type 1 receptor(VEGFR1) is up-regulated by SMC-MR. Together, these effects of SMC-MR activation lead to significant effects on vessel function, including: increases in vascular tone, vasoconstriction, SMC proliferation, SMC migration, vascular fibrosis and vascular stiffness. Ultimately, SMC-MR activation results in end-organ damage such as high blood pressure, coronary vascular dysfunction, cardiac interstitial fibrosis, alterations in renal hemodynamics and kidney failure. AngII; Angiotensin II. ROS; reactive oxygen species. ROCK; Rho-associated kinase. Ca; calcium. SMC; smooth muscle cell. LV; left ventricle.