0346: Aldosterone promotes cardiac endothelial cells proliferation and angiogenesis

Background The mineralocorticoid receptor (MR) and its ligand, aldosterone (aldo), are involved in cardiac diseases. However, the cardiomyocyte-MR regulated processes leading to these injuries are still unclear. Objective To identify new aldosterone-regulated functions involved in cardiac diseases. Methods and Results Double transgenic mice overexpressing MR in cardiomyocytes (DT) and their controls (CT) were treated for 7 days with aldosterone (60 μg/kg/day; n = 6-9 / group) and a genome microarray analysis was performed. In CT mice, aldo regulated 70 genes. In DT mice, aldo induced much more genes (343). To identify the biological processes modulated by aldo, a gene ontology analysis was performed. The majority of aldosteroneregulated genes were involved in cell division, as shown by the relative expression of Cycline B1 and Cdk1 (Cycline; CT untreated 1 ± 0.02, CT aldotreated 2.1 ± 0.5; Cdk1; CT untreated 1 ± 0.05, CT aldo-treated 2.2 ± 0.4). Moreover, the Ki-67 index of aldo-treated mice (CT and DT) was higher than in non-treated ones (% of positive Ki-67 nuclei vs total nuclei; CT untreated 15±4, CT aldo-treated 51±12%; DT untreated 29 ± 5, DT aldo-treated 61 ± 19%). Co-staining of Ki-67 with caveolin 1 revealed that the cycling cells were endothelial cells. Ki-67 index was increased in an experimental model of heart failure (transverse aortic constriction: TAC) in rats. Eplerenone (eple), a MR blocker, prevented this increase (% of positive Ki-67 nuclei vs total nuclei; sham 26 ± 3, TAC 42 ± 5, TAC+eple 23 ± 6%). Conclusion Aldosterone induces cardiac endothelial cells proliferation in vivo and underlines the role of cardiomyocyte-MR activation in this process. Perspectives Favre and collaborators (AJP 2011) reported that cardiomyocyte- MR activation is involved in coronary endothelial dysfunction, via pathways of oxidative stress. It appears interesting to study if the cardiac endothelial cells proliferation induced by aldo is oxidative stress dependent.