Aldosterone impairs bone marrow-derived progenitor cell formation

Takeshi Marumo, Hideki Uchimura, Matsuhiko Hayashi, Keiichi Hishikawa, Toshiro Fujita

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Aldosterone has been suggested recently to cause vascular injury by directly acting on the vasculature, in addition to causing injury by raising the blood pressure. Bone marrow-derived endothelial progenitor cells (EPCs) have been shown to exert an important role in the repair of the endothelium. In addition, cell-based therapy using EPCs is emerging as a novel therapeutic strategy for myocardial and peripheral vascular diseases. However, impaired formation and function of EPCs has been observed in patients with risk factors for cardiovascular diseases. We evaluated the possible effects of aldosterone on EPCs by examining the progenitor cell formation from bone marrow mononuclear cells ex vivo. Aldosterone (10 to 1000 nmol/L) reduced the formation of progenitor cells in a concentration-dependent manner. This effect of aldosterone was attenuated by cotreatment with spironolactone. Aldosterone reduced the mRNA levels of vascular endothelial growth factor (VEGF) receptor (VEGFR) 2 without having any effect on the production of VEGF or mRNA levels of VEGF and hepatocyte growth factor in the progenitor cells. However, the expression of stromal-derived growth factor 1 mRNA was paradoxically increased. Consistent with the downregulation of VEGFR-2, VEGF-induced phosphorylation of Akt was abolished in the progenitor cells after aldosterone treatment. N-acetylcysteine, an antioxidant, attenuated the inhibitory effects of aldosterone. These data indicate that aldosterone inhibits the formation of bone marrow-derived progenitor cells, at least partly, by attenuating VEGFR-2 expression and the subsequent Akt signaling. Reduction of aldosterone levels, blockade of mineralocorticoid receptor, and/or cotreatment with antioxidants may, therefore, enhance vascular regeneration by EPCs.

Original languageEnglish
Pages (from-to)490-496
Number of pages7
JournalHypertension
Volume48
Issue number3
DOIs
Publication statusPublished - 2006 Sep 1

Keywords

  • Aldosterone
  • Endothelium
  • Mineralocorticoids
  • Oxidative stress

ASJC Scopus subject areas

  • Internal Medicine

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    Marumo, T., Uchimura, H., Hayashi, M., Hishikawa, K., & Fujita, T. (2006). Aldosterone impairs bone marrow-derived progenitor cell formation. Hypertension, 48(3), 490-496. https://doi.org/10.1161/01.HYP.0000235681.25685.cf