Aldosterone promotes cardiac endothelial cell proliferation in vivo

• Published in: Journal of the American Heart Association Vol. 4; no. 1; p. e001266
• Main Authors: Gravez, Basile, Tarjus, Antoine, Pelloux, Véronique, Ouvrard-Pascaud, Antoine, Delcayre, Claude, Samuel, Janelise, Clément, Karine, Farman, Nicolette, Jaisser, Fréderic, Messaoudi, Smail
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 06-01-2015
• Subjects: Aldosterone - pharmacology; Analysis of Variance; Animals; Blood Pressure - physiology; Cell Proliferation - drug effects; Cell Proliferation - genetics; Cells, Cultured; Disease Models, Animal; Endothelial Cells - drug effects; Endothelial Cells - metabolism; Gene Expression Profiling; Heart Failure - metabolism; Heart Failure - physiopathology; Humans; Male; Mice; Mice, Inbred Strains; Original Research; Statistics, Nonparametric; proliferation; pressure overload; aldosterone; heart
• ISSN: 2047-9980; 2047-9980
• DOI: 10.1161/jaha.114.001266

Experimentally, aldosterone in association with NaCl induces cardiac fibrosis, oxidative stress, and inflammation through mineralocorticoid receptor activation; however, the biological processes regulated by aldosterone alone in the heart remain to be identified.
Mice were treated for 7 days with aldosterone, and then cardiac transcriptome was analyzed. Aldosterone regulated 60 transcripts (51 upregulated and 9 downregulated) in the heart (fold change ≥1.5, false discovery rate <0.01). To identify the biological processes modulated by aldosterone, a gene ontology analysis was performed. The majority of aldosterone-regulated genes were involved in cell division. The cardiac Ki-67 index (an index of proliferation) of aldosterone-treated mice was higher than that of nontreated mice, confirming microarray predictions. Costaining of Ki-67 with vinculin, CD68, α-smooth muscle actin, CD31, or caveolin 1 revealed that the cycling cells were essentially endothelial cells. Aldosterone-induced mineralocorticoid receptor-dependent proliferation was confirmed ex vivo in human endothelial cells. Moreover, pharmacological-specific blockade of mineralocorticoid receptor by eplerenone inhibited endothelial cell proliferation in a preclinical model of heart failure (transverse aortic constriction).
Aldosterone modulates cardiac gene expression and induces the proliferation of cardiac endothelial cells in vivo.