Regulation of circulating progenitor cells in left ventricular dysfunction.

Area of Science:

• Cardiovascular Biology
• Hematology
• Endocrinology

Background:

• Circulating progenitor cells, including CD34+ cell subsets, are reduced in cardiovascular disease (CVD).
• The specific factors mediating these reductions in progenitor cells are not well understood.
• Neurohumoral factors are investigated as potential regulators of progenitor cell populations in vivo.

Purpose of the Study:

• To investigate the role of neurohumoral factors, specifically mineralocorticoids, in regulating circulating progenitor cells.
• To determine the effect of left ventricular (LV) dysfunction on progenitor cell subsets.
• To assess the impact of mineralocorticoid excess on hematopoietic progenitor cells (HPCs) and endothelial progenitor cells (EPCs).

Main Methods:

• Utilized canine models of left ventricular (LV) dysfunction, including pacing-induced and hypertensive renal wrap models.
• Quantified circulating CD34+ cell subsets, specifically HPCs (CD34+/CD45(dim)/VEGFR2-) and EPCs (CD34+/CD45-/VEGFR2+).
• Administered deoxycorticosterone acetate (DOCA) to normal dogs to study the effects of exogenous mineralocorticoid excess.

Main Results:

• Pacing-induced LV dysfunction led to a decrease in HPCs, correlating with plasma aldosterone levels.
• Mineralocorticoid excess induced by DOCA administration significantly reduced HPCs in peripheral blood.
• No significant changes were observed in endothelial progenitor cells (EPCs) in either model.
• DOCA treatment in normal dogs decreased HPCs in peripheral blood but not bone marrow, linked to reduced telomerase activity.

Conclusions:

• This study demonstrates that both endogenous and exogenous mineralocorticoid excess reduce hematopoietic progenitor cells (HPCs).
• Mineralocorticoids may accelerate the senescence of progenitor cells, leading to a decline in their numbers.
• These findings suggest a novel mechanism linking mineralocorticoid activity to reduced progenitor cell populations in conditions like cardiovascular disease.