Comprehensive analysis of aldosterone-regulated genes in human vascular cells

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A series of studies have demonstrated that endothelial cell is one of the target tissues of aldosterone. Here, we have conducted a comprehensive gene expression analysis of aldosterone-inducible genes in human endothelial cell lines stably expressing human mineralocorticoid receptor(MR) by bicistronic retroviral system(MR-EAhy). We found that aldosterone in physiological concentrations robustly induced MR-dependent transcriptional response in MR-EAhy. By DNA microarray analysis, we validated 12 aldosterone-inducible genes up-regulated(FKBP5, DDIT4, CCL23, NEDD9, EPS8, ESM-1, AKAP12, ERRFI1, ANGPTL4, S1P3, IGFBP3, SNF1LK) among which at least 7 genes(FKBP5, CCL23, NEDD9, ESM-1, ERRFI1, ANGPTL4, IGFBP3, SNF1LK) were confirmed to their upregulation at protein levels. In addition, the mRNA expressions of ESM1, SNF1LK, ANGPTL4 were upregulated in vascular tissue from aldosterone-induced hypertensive rats, suggesting the pathophysiological relevance of these genes in aldosterone-induced vascular injury. In conclusion, using MR stably-expressed human endothelial cell lines, we identified a variety of aldosterone-inducible genes, with their possible roles in the development and/or the protection for aldosterone-induced vascular injury.