Mitral valve prolapse (MVP) is one of the most common valvular disorders. Aldosterone (Aldo) promotes fibrosis in the myocardium, and MR (mineralocorticoid receptor) antagonists (MRAs) improve cardiac function by decreasing cardiac fibrosis. This study aimed to investigate the role of the Aldo/MR in the fibromyxomatous modifications associated with MVP.

Aldo enhanced valvular interstitial cell activation markers and induced endothelial-mesenchymal transition in valvular endothelial cells, resulting in increased proteoglycan secretion. MRA blocked all of the above effects. Cytokine arrays showed CT-1 (cardiotrophin-1) to be a mediator of Aldo-induced valvular interstitial cell activation and proteoglycan secretion and CD (cluster of differentiation) 14 a mediator of Aldo-induced endothelial-mesenchymal transition and proteoglycan secretion in valvular endothelial cells. Endothelial-specific MR deletion prevents fibromyxomatous changes induced by nordexfenfluramine administration. These findings demonstrate, for the first time, that the Aldo/MR pathway regulates the phenotypic, molecular, and histological changes of valvular interstitial cells and valvular endothelial cells associated with MVP development. 

In conclusion, Aldo/MR modulates mitral valve remodeling, inducing VIC activation and EndMT, and increasing proteoglycan deposition. We showed that MRA reduces mitral valve alterations in an experimental model of MVP, suggesting a novel therapeutic approach to reduce mitral valve remodeling associated with MVP.