Abstract 1946: Hyperaldosteronism Mediates Reduced Circulating Progenitor Cell Counts in Cardiac Failure
Background: Reduced numbers of circulating progenitor cells have been demonstrated in cardiovascular disease. Recent data suggest that aldosterone may impair progenitor cell function in vitro. To determine whether aldosterone levels might regulate circulating progenitor cell (CPC) counts in vivo, we studied two canine models of left ventricular dysfunction and correlated CPC counts in the setting of elevated endogenous and exogenous mineralocorticoids.
Methods: CD34+ circulating progenitor cell (CPC) counts were enumerated at baseline and biweekly in an 8 week renal wrap model of diastolic dysfunction (n=10), where dogs were randomized to deoxycorticosterone acetate (DOCA) treatment 1mg/kg/day from week 5. CPC counts were also analyzed in a paced model of systolic LV dysfunction at baseline and 10 days later (n=10). Serum aldosterone, ANP and BNP levels were measured in the paced dogs at 10 days.
Results: A significant decline was noted in CD34 counts in both groups with progressive cardiac failure (p<0.01). In the RW group, addition of DOCA accelerated the decline in CD34 counts to produce a significant difference in CD34 counts between treated and untreated dogs at 8 weeks (34±6 vs.11±1 CD34+ cells/100μL whole blood, p<0.01). CD34 counts in the RW group correlated significantly with LV radial wall strain (R=−0.59, p<0.01) and collagen content (R=−0.71, p<0.05), indices of increased wall stiffness and fibrosis. In the paced animals, a significant correlation was noted between plasma aldosterone levels and the change in CD34 count between baseline and the acute study at 10 days (R=−0.66, p<0.05).
Conclusion: This is the first study to demonstrate a reduction in circulating cells in models of canine left ventricular dysfunction. Furthermore, the association with exogenous and endogenous mineralocorticoids provides a potential mechanism for the reduction. This may represent a toxic effect of aldosterone on the bone marrow and impaired release of progenitor cells into the circulation. This observation suggests yet another beneficial potential mode of action for aldosterone antagonists in congestive cardiac failure which warrants further investigation.