Related Experiment Video
Updated: Apr 18, 2026
Induction of Atherosclerotic Plaques Through Activation of Mineralocorticoid Receptors in Apolipoprotein E-deficient Mice
Published on: September 26, 2018
Aldosterone promotes cardiac endothelial cell proliferation in vivo
Basile Gravez1, Antoine Tarjus1, Véronique Pelloux2
1Inserm U1138, Team 1, 15 rue de l'école de médecine, Paris, France (B.G., A.T., N.F., F.J., S.M.).
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, 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.
Insights
Aldosterone alone, not just with salt, drives heart cell division, primarily in endothelial cells. This mineralocorticoid receptor-dependent process is a novel finding in cardiac biology.
Area of Science:
- Cardiovascular Biology
- Endocrinology
- Molecular Cardiology
Background:
- Aldosterone in conjunction with NaCl causes cardiac fibrosis, oxidative stress, and inflammation via mineralocorticoid receptor activation.
- The specific biological processes regulated by aldosterone alone in the heart were previously unidentified.
Purpose of the Study:
- To elucidate the cardiac biological processes regulated by aldosterone independently.
- To investigate the role of aldosterone in cardiac cell proliferation.
Main Methods:
- Cardiac transcriptome analysis in mice treated with aldosterone.
- Gene ontology analysis to identify biological processes.
- Immunohistochemical staining for Ki-67 to assess cell proliferation.
- Ex vivo studies using human endothelial cells.
- Preclinical heart failure model (transverse aortic constriction) with eplerenone treatment.
Main Results:
- Aldosterone modulated 60 cardiac transcripts (51 upregulated, 9 downregulated) in mice.
- Gene ontology analysis revealed aldosterone-regulated genes are predominantly involved in cell division.
- Aldosterone treatment significantly increased the cardiac Ki-67 proliferation index.
- Proliferating cells were identified as endothelial cells.
- Aldosterone-induced mineralocorticoid receptor-dependent endothelial cell proliferation was confirmed ex vivo and inhibited by eplerenone in vivo.
Conclusions:
- Aldosterone independently modulates cardiac gene expression.
- Aldosterone induces cardiac endothelial cell proliferation in vivo.
- Mineralocorticoid receptor blockade inhibits aldosterone-induced endothelial cell proliferation.
Related Concept Videos
01:26Heart Failure Drugs: Inhibitors of Renin-Angiotensin System
01:30Antihypertensive Drugs: Angiotensin II Receptor Blockers
01:30Antihypertensive Drugs: Angiotensin-Converting Enzyme Inhibitors
01:33Hormonal Regulation
01:17Antihypertensive Drugs: Action of β1 Blockers
01:45Endocrine Signaling