Aldosterone Promotes Cardiac Endothelial Cell Proliferation In Vivo

Authors
Basile Gravez, MSc; Antoine Tarjus, PhD; Véronique Pelloux, MSc; Antoine Ouvrard?Pascaud, PhD; Claude Delcayre, PhD; Janelise Samuel, MD, PhD; Karine Clément, MD, PhD; Nicolette Farman, MD, PhD; Fréderic Jaisser, MD, PhD; Smail Messaoudi, PhD

Lab
INSERM?UMR 1166, Pitié?Salpêtrière, Paris, France

Journal
J Am Heart Assoc.

Abstract
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 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, ??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.

BIOSEB Instruments Used:
BP-2000 Blood Pressure Analysis System (BP-2000-M6-R4),BP-2000 Blood Pressure Analysis System (BP-2000-M-4)