Pleiotropic Effect of Aldosterone on Human Endothelial Cells In Vitro

Abstract

Aim: To investigate the effect of aldosterone and its antagonists on cell behavior and gene modulation in human endothelial cells. Methods and Results: Exposure of HBMEC to 100 nM aldosterone reduced the subsequent organization and assembly of cells into capillary-like networks, capillary length and cell multiplication but cell migration to the wound edge was not affected by the agonist. Eplerenone (400 nM) partially reversed the inhibitory effect of the agonist on capillary length, the number of capillary networks, as well as cell multiplication; the antagonist also inhibited the migration of HBMEC in a wound healing assay. Aldactone was more potent than eplerenone in most of the tests, due possibly to the fact that the former derivative is not specific to the MCR but activates other classes of steroid receptors as well. Transcriptional modulation by aldosterone was analyzed using a gene array technique that screened 1800 genes related to cytokines, monokines, growth factors, angiogenic effectors, cell metabolism, growth and malignant transformation. Evidence is provided here for the simultaneous upregulation of 36 mRNAs, and concurrent downregulation of 29 mRNAs, in endothelial cells exposed for 8 h to 100 nM aldosterone. Conclusions: Aldosterone inhibits cell migration, network formation, and cell proliferation in vitro, possibly via a pleiotropic effect on transcription modulation in human endothelial cells.