title: Aldosterone promotes cardiac endothelial cell proliferation in vivo.
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.
  
  
  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, 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.
authors.affiliation: Inserm U1138, Team 1, 15 rue de l'école de médecine, Paris, France (B.G., A.T., N.F., F.J., S.M.).
authors.forename: Basile
authors.initials: B
authors.lastname: Gravez
authors.affiliation: Inserm U1138, Team 1, 15 rue de l'école de médecine, Paris, France (B.G., A.T., N.F., F.J., S.M.).
authors.forename: Antoine
authors.initials: A
authors.lastname: Tarjus
authors.affiliation: INSERM-UMR 1166 Team 6- GH Pitié-Salpêtrière, 83 Bd de l'hôpital, Paris, France (P., K.C.).
authors.forename: Véronique
authors.initials: V
authors.lastname: Pelloux
authors.affiliation: UMR 644 Inserm-Université de Rouen. 22, Boulevard Gambetta, Rouen, France (A.O.P.).
authors.forename: Antoine
authors.initials: A
authors.lastname: Ouvrard-Pascaud
authors.affiliation: Inserm U942, 41 Boulevard de la chapelle, Paris, France (C.D., J.S.).
authors.forename: Claude
authors.initials: C
authors.lastname: Delcayre
authors.affiliation: Inserm U942, 41 Boulevard de la chapelle, Paris, France (C.D., J.S.).
authors.forename: Janelise
authors.initials: J
authors.lastname: Samuel
authors.affiliation: INSERM-UMR 1166 Team 6- GH Pitié-Salpêtrière, 83 Bd de l'hôpital, Paris, France (P., K.C.).
authors.forename: Karine
authors.initials: K
authors.lastname: Clément
authors.affiliation: Inserm U1138, Team 1, 15 rue de l'école de médecine, Paris, France (B.G., A.T., N.F., F.J., S.M.).
authors.forename: Nicolette
authors.initials: N
authors.lastname: Farman
authors.affiliation: Inserm U1138, Team 1, 15 rue de l'école de médecine, Paris, France (B.G., A.T., N.F., F.J., S.M.).
authors.forename: Fréderic
authors.initials: F
authors.lastname: Jaisser
authors.affiliation: Inserm U1138, Team 1, 15 rue de l'école de médecine, Paris, France (B.G., A.T., N.F., F.J., S.M.).
authors.forename: Smail
authors.initials: S
authors.lastname: Messaoudi
mesh_terms: D000450:Aldosterone / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects* / Q000235:genetics*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D020869:Gene Expression Profiling; D006333:Heart Failure / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018709:Statistics, Nonparametric
chemical_list: D000450:Aldosterone
keywords: aldosterone; heart; pressure overload; proliferation