Aldosterone impairs bone marrow-derived progenitor cell formation

Area of Science:

• Cardiovascular Biology
• Endothelial Cell Biology
• Regenerative Medicine

Background:

• Aldosterone contributes to vascular injury beyond elevating blood pressure.
• Endothelial progenitor cells (EPCs) are crucial for vascular repair and are a focus of cell-based therapies.
• EPC dysfunction is observed in cardiovascular disease risk factors.

Purpose of the Study:

• To investigate the direct effects of aldosterone on the formation and function of bone marrow-derived EPCs.
• To elucidate the molecular mechanisms underlying aldosterone's impact on EPCs.

Main Methods:

• Ex vivo assessment of progenitor cell formation from bone marrow mononuclear cells.
• Concentration-dependent treatment with aldosterone and spironolactone.
• Measurement of growth factor and receptor mRNA levels (VEGF, VEGFR-2, HGF, SDF-1).
• Analysis of VEGF-induced Akt phosphorylation and effect of N-acetylcysteine.

Main Results:

• Aldosterone reduced EPC formation in a concentration-dependent manner, an effect blunted by spironolactone.
• Aldosterone decreased VEGFR-2 mRNA levels but not VEGF or HGF.
• VEGF-induced Akt phosphorylation was abolished post-aldosterone treatment.
• N-acetylcysteine attenuated the inhibitory effects of aldosterone on EPC formation.

Conclusions:

• Aldosterone inhibits bone marrow-derived EPC formation, partly via VEGFR-2 downregulation and impaired Akt signaling.
• Strategies like reducing aldosterone, blocking mineralocorticoid receptors, or using antioxidants may improve vascular regeneration by EPCs.