Abstract 1884: Rosuvastatin Activates Circulating Stem and Progenitor Cells, Promotes Endogenous Tissue Regeneration, and Improves Central Hemodynamics in Patients With Chronic Heart Failure
Endogenous regeneration is impaired in patients (pts) with chronic heart failure (CHF), which results in peripheral, but also central hemodynamic alterations. Statins are known to promote stem cell release and enhance phosphorylation of the survival kinase AKT, which is associated with an increased cardiomyocyte contractility. Therefore, the present study aimed to investigate the effects of rosuvastatin on number and function of stem and circulating progenitor cells (CPC), their contribution to tissue neovascularization, and its impact on endothelial function and central hemodynamics in pts with CHF.
Methods: Forty-two pts with CHF (EF 30±1%; n=12 ischemic, and n=30 dilative cardiomyopathy) were randomized to 12 weeks (wks) of 40 mg rosuvastatin daily or placebo therapy (P) in a double-blind manner. At begin (B) and at 12 wks, the number of circulating CD34+ stem cells and CD34/KDR+ CPCs was measured, functional capacity of CPCs was assessed by migration and matrigel assay, and capillary density of skeletal muscle (SM) was quantified. Muscular phosphorylation levels of AKT were determined. Flow-mediated dilatation (FMD) was measured by high-resolution ultrasound and ejection fraction (EF) assessed by echocardiography.
Results: Rosuvastatin increased the number of CPCs by +132% (p<0.05 vs P), improved their migratory capacity by +83% and their integrative capacity by +91% (p<0.05 vs P), respectively. FMD recovered from +197±25 μm at B to +478±50 μm at 12 wks in the rosuvastatin group. The rosuvastatin-mediated increase in circulating CD34+ cells was closely correlated to the improvement in FMD (r=0.70, p<0.01) and the augmentation in capillary density of SM (r=0.76, p<0.01). Rosuvastatin enhanced muscular AKT phosphorylation 2.5fold, which was associated with a gain in EF by + 8±1% (p<0.05 vs P). All parameters remained unchanged in the placebo group.
Conclusion: In pts with CHF, rosuvastatin improves left-ventricular ejection fraction, promotes skeletal muscle neovascularization, and enhances endothelial function, partially through activation of circulating stem and progenitor cells. Therefore, rosuvastatin might be considered as a therapeutic strategy to induce endogenous tissue regeneration and improve central hemodynamics in CHF.