Abstract 2170: Rosuvastatin Promotes Neovascularization in the Skeletal Muscle in Patients with Chronic Heart Failure
Bone marrow-derived stem cells are known to contribute to endogenous tissue regeneration. However, in patients (pts) with chronic heart failure (CHF), the number of circulating stem cells was found to be reduced suggestive of an attenuation of endogenous tissue repair. Given the beneficial effects of statins with regard to progenitor cell release and function, aim of the present trial was to elucidate, whether rosuvastatin influences neovascularization in the skeletal muscle through activation of circulating progenitor cells (CPC) in pts with CHF.
Methods: Forty pts with CHF (LVEF 30±1%) due to ischemic (n=12) or dilated cardiomyopathy (n=28) were randomized to 12 weeks of 40 mg rosuvastatin daily or placebo therapy in a double-blind manner. At baseline and 12 weeks, plasma VEGF levels were assessed by ELISA. AcLDL/lectin+ CPCs were recovered from blood-derived mononuclear cells by cell culture and counted using FACS. Functional capacity of CPCs was determined by migration and matrigel assay. Percutanous biopsies of the vastus lateralis muscle were obtained, the number of CD34+ stem cells in skeletal muscle and capillary density were quantified applying immunohistochemistry.
Results: Rosuvastatin increased circulating VEGF levels from 67±13 pg/mL at baseline to 95±20 pg/mL at 12 weeks (p<0.05 vs placebo). This was associated with an elevation in CPC number by 409±138% (p<0.01 vs placebo), an augmentation of CPC migratory capacity from 1.6±0.5 to 2.8±0.6 cells per 100 plated cells (p<0.05 vs placebo) and their ability to integrate into endothelial networks from 1.5±0.5 to 2.9±0.6 cells per 100 coronary endothelial cells (p<0.05 vs placebo). Capillary density in skeletal muscle increased by 14±3% in the rosuvastatin group (p<0.05 vs placebo), which was partially the result of an enhanced homing of CD34+ cells in skeletal muscle (from 3.7±0.7 to 7.5±1.3 cells per high-power field, p<0.05 vs placebo). All parameters remained unchanged in the placebo group.
Conclusion: In pts with CHF, rosuvastatin increases the amount of CPCs, improves their functional capacity thereby promoting neovascularization in the skeletal muscle. Therefore, rosuvastatin might have the therapeutic potential to ameliorate endogenous tissue regeneration in CHF.