Increase in circulating endothelial progenitor cells by statin therapy in patients with stable coronary artery disease

Background-Therapeutic neovascularization may constitute an important strat egy to salvage tissue from critical ischemia. Circulating bone marrow-deriv ed endothelial progenitor cells (EPCs) were shown to augment the neovascula rization of ischemic tissue. In addition to lipid-lowering activity, hydrox ymethyl glutaryl coenzyme A reductase inhibitors (statins) reportedly promo te the neovascularization of ischemic tissue in normocholesterolemic animal s. Methods and Results-Fifteen patients with angiographically documented stabl e coronary artery disease (CAD) were prospectively treated with 40 mg of at orvastatin per day for 4 weeks. Before and weekly after the initiation of s tatin therapy, EPCs were isolated from peripheral blood and counted. In add ition, the number of hematopoietic precursor cells positive for CD34, CD133 , and CD34/kinase insert domain receptor was analyzed. Statin treatment of patients with stable CAD was associated with an approximate to1.5-fold incr ease in the number of circulating EPCs by 1 week after initiation of treatm ent; this was followed by sustained increased levels to approximate to3-fol d throughout the 4-week study period. Moreover, the number of CD34/kinase i nsert domain receptor-positive hematopoietic progenitor cells was significa ntly augmented after 4 weeks of therapy. Atorvastatin treatment increased t he further functional activity of EPCs, as assessed by their migratory capa city. Conclusion-The results of the present study define a novel mechanism of act ion of statin treatment in patients with stable CAD: the augmentation of ci rculating EPCs with enhanced functional activity. Given the well-establishe d role of EPCs of participating in repair after ischemic injury, stimulatio n of EPCs by statins may contribute to the clinical benefit of statin thera py in patients with CAD.