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Mineralocorticoid receptor activation promotes vascular cell calcification.
- Source :
-
Arteriosclerosis, thrombosis, and vascular biology [Arterioscler Thromb Vasc Biol] 2007 Apr; Vol. 27 (4), pp. 799-805. Date of Electronic Publication: 2007 Jan 18. - Publication Year :
- 2007
-
Abstract
- 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.<br />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.<br />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.
- Subjects :
- 11-beta-Hydroxysteroid Dehydrogenase Type 2 metabolism
Adrenal Cortex Hormones pharmacology
Aldosterone pharmacology
Alkaline Phosphatase metabolism
Animals
Aorta
Bone Morphogenetic Protein 2
Bone Morphogenetic Proteins metabolism
Calcinosis enzymology
Calcinosis metabolism
Cattle
Cells, Cultured
Coronary Vessels
Humans
Minerals metabolism
Muscle, Smooth, Vascular enzymology
Muscle, Smooth, Vascular metabolism
Muscle, Smooth, Vascular pathology
Myocytes, Smooth Muscle enzymology
Myocytes, Smooth Muscle metabolism
Receptors, Mineralocorticoid drug effects
Signal Transduction
Transforming Growth Factor beta metabolism
Vascular Diseases enzymology
Vascular Diseases metabolism
Calcinosis etiology
Receptors, Mineralocorticoid metabolism
Vascular Diseases etiology
Subjects
Details
- Language :
- English
- ISSN :
- 1524-4636
- Volume :
- 27
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Arteriosclerosis, thrombosis, and vascular biology
- Publication Type :
- Academic Journal
- Accession number :
- 17234727
- Full Text :
- https://doi.org/10.1161/01.ATV.0000258414.59393.89