Statin therapy in patients withcoronary artery disease improves the impaired endothelialprogenitor cell differentiation into cardiomyogeniccells

Human endothelial progenitor cells (EPCs) can differentiate intocardiomyogenic cells in vitro. We tested the effects of statin therapy on thedifferentiation rate of EPCs from patients with coronary artery disease (CAD),who may benefit from autologous cell therapy.EPCs from 3 age-matched groups were tested: No CAD (n = 13), CADpatients with (n = 10) or without (n = 16) statin therapy. From 4 CAD patients,EPCs were tested before and after 4 weeks of therapy with 20 mg atorvastatin.After 6 days of co-culture with rat neonatal cardiomyocytes, EPC differentiationwas quantified by immunostaining for -sarcomeric actinin flowcytometry analysis. After 6 days of co-culture, the percentage of -sarcomericactinin–positive EPCs was significantly (p = 0.014) higher in EPCs fromadults without CAD (8.07% ± 1.48% of EPCs) compared to EPCs from CADpatients without statin (3.56% ± 0.72%). Importantly, patients with statintherapy revealed significantly higher numbers of -sarcomeric actinin-positiveEPCs (6.36% ± 0.69%, p = 0.01) compared to CAD patients withoutstatin. In addition, statin therapy resulted in a significant (p = 0.017) increaseof EPC differentiation in all 4 CAD patients investigated before and 4 weeksafter statin therapy. The survival of EPCs did not differ between the differentgroups suggesting that the regulation of EPC differentiation is not secondaryto altered EPC survival. In vitro, EPC treatment with 0.1 µM atorvastatin didnot affect EPC differentiation (116.15% ± 49.11% of control).EPCs from patients with CAD display impaired differentiation into cardiomyogeniccells. This defect can be improved by in vivo, statin therapy.