Aldosterone activation of the mineralocorticoid receptor promotes osteoblastic differentiation and mineralization of vascular smooth muscle cells independent of BMP2 signaling.
Does aldosterone promote osteoblastic differentiation and mineralization in vascular smooth muscle cells?
Aldosterone promotes vascular calcification via mineralocorticoid receptor activation independent of BMP2 signaling, providing a mechanistic rationale for the cardiovascular benefits of MR antagonists.
OBJECTIVE: Clinical studies demonstrate that mineralocorticoid receptor (MR) antagonism improves outcomes in cardiovascular patients and that vascular calcification correlates with adverse cardiac events. We have recently demonstrated that human vascular smooth muscle cells (VSMCs) express functional MRs that, in response to aldosterone, modulate expression of osteogenic genes including alkaline phosphatase (ALP) and bone morphogenetic protein-2 (BMP2). This study examines the effects of MR activation by aldosterone on the process of in vitro vascular calcification. METHODS AND RESULTS: Using immunoblotting and adenoviral promoter-reporter assays, we demonstrated that calcifying vascular cells (CVCs), an in vitro model of vascular calcification, express MRs that mediate both aldosterone- and cortisol-stimulated gene transcription. In this model, aldosterone stimulated ALP activity, an early marker of osteoblastic differentiation, as well as mineralization. Aldosterone antagonism with spironolactone abolished both effects implicating CVC MRs in the mechanism of aldosterone-stimulated vascular calcification. Inhibition of BMP2 signaling by overexpression of dominant negative BMP2 receptor did not attenuate aldosterone-induced osteoblastic differentiation. CONCLUSIONS: Aldosterone activation of MR promotes osteoblastic differentiation and mineralization of VSMCs independent of BMP2 signaling. These data provide a mechanistic link between hormone-mediated VSMC MR activation and vascular calcification, two processes associated with increased risk of cardiovascular ischemic events in humans.
Jaffe et al. (Fri,) conducted a other in Vascular calcification. Aldosterone vs. Spironolactone was evaluated on Osteoblastic differentiation (ALP activity) and mineralization. Aldosterone activation of the mineralocorticoid receptor promotes osteoblastic differentiation and mineralization of vascular smooth muscle cells independent of BMP2 signaling.