The toxic effects of aldosterone on the vasculature, and in particular on the endothelial layer, have been proposed as having an important role in the cardiovascular pathology observed in mineralocorticoid-excess states. In order to characterize the genomic molecular mechanisms driving the aldosterone-induced endothelial dysfunction, we performed an expression microarray on transcripts obtained from both human umbilical vein endothelial cells and human coronary artery endothelial cells stimulated with 10 - 7 M aldosterone for 18 h. The results were then subjected to qRT-PCR confirmation, also including a group of genes known to be involved in the control of the endothelial function or previously described as regulated by aldosterone. The state of activation of the mineralocorticoid receptor was investigated by means of a luciferase-reporter assay using a plasmid encoding a mineralocorticoid and glucocorticoid-sensitive promoter. Aldosterone did not determine any significant change in gene expression in either cell type both in the microarray and in the qRT-PCR analysis. The luciferase-reporter assay showed no activation of the mineralocorticoid receptor following aldosterone stimulation. The status of nonfunctionality of the mineralocorticoid receptor expressed in cultured human umbilical and coronary artery endothelial cells does not allow aldosterone to modify gene expression and provides evidence against either a beneficial or harmful genomic effect of aldosterone on healthy endothelial cells.

Aldosterone does not modify gene expression in human endothelial cells

WILLIAMS, Tracy Ann;Morello F;MONTICONE, Silvia;BRIZZI, Maria Felice;DENTELLI, Patrizia;VEGLIO, Franco;MULATERO, Paolo
2012

Abstract

The toxic effects of aldosterone on the vasculature, and in particular on the endothelial layer, have been proposed as having an important role in the cardiovascular pathology observed in mineralocorticoid-excess states. In order to characterize the genomic molecular mechanisms driving the aldosterone-induced endothelial dysfunction, we performed an expression microarray on transcripts obtained from both human umbilical vein endothelial cells and human coronary artery endothelial cells stimulated with 10 - 7 M aldosterone for 18 h. The results were then subjected to qRT-PCR confirmation, also including a group of genes known to be involved in the control of the endothelial function or previously described as regulated by aldosterone. The state of activation of the mineralocorticoid receptor was investigated by means of a luciferase-reporter assay using a plasmid encoding a mineralocorticoid and glucocorticoid-sensitive promoter. Aldosterone did not determine any significant change in gene expression in either cell type both in the microarray and in the qRT-PCR analysis. The luciferase-reporter assay showed no activation of the mineralocorticoid receptor following aldosterone stimulation. The status of nonfunctionality of the mineralocorticoid receptor expressed in cultured human umbilical and coronary artery endothelial cells does not allow aldosterone to modify gene expression and provides evidence against either a beneficial or harmful genomic effect of aldosterone on healthy endothelial cells.
44
3
234
238
mineralocorticoid - endothelial dysfunction - genomic; aldosterone
endothelial dysfunction; genomic; mineralocorticoid; Aldosterone; Cell Line; Endothelial Cells; Gene Expression; Genes, Reporter; Human Umbilical Vein Endothelial Cells; Humans; Mineralocorticoids; Receptors, Mineralocorticoid; Biochemistry; Endocrinology; Clinical Biochemistry; Biochemistry (medical); Endocrinology, Diabetes and Metabolism
Verhovez A; Williams TA; Morello F; Monticone S; Brizzi MF; Dentelli P; Fallo F; Fabris B; Amenta F; Gomez-Sanchez C; Veglio F; Mulatero P
File in questo prodotto:
File Dimensione Formato  
HMR_2011 Verhovez Endo Aldo.pdf

Accesso riservato

Tipo di file: POSTPRINT (VERSIONE FINALE DELL’AUTORE)
Dimensione 222.51 kB
Formato Adobe PDF
222.51 kB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/93558
Citazioni
  • ???jsp.display-item.citation.pmc??? 3
  • Scopus 8
  • ???jsp.display-item.citation.isi??? 8
social impact