Aldosterone promotes cardiac endothelial cell proliferation in vivo

Background: 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. methods and results: 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 aldosteroneregulated 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). conclusions: aldosterone modulates cardiac gene expression and induces the proliferation of cardiac endothelial cells in vivo. © 2015 the authors.