HMG-CoA reductase inhibitors (statins) increase endothelial progenitor cells via the PI 3-kinase/Akt pathway

HMG-CoA reductase inhibitors (statins) have been developed as lipid-lowerin g drugs and are well established to reduce morbidity and mortality from cor onary artery disease. Here we demonstrate that statins potently augment end othelial progenitor cell differentiation in mononuclear cells and CD34-posi tive hematopoietic stem cells isolated from peripheral blood. Moreover, tre atment of mice with statins increased c-kit(+)/Sca-1(+)-positive hematopoie tic stem cells in the bone marrow and further elevated the number of differ entiated endothelial progenitor cells (EPCs). Statins induce EPC differenti ation via the PI 3-kinase/Akt (PI3K/Akt) pathway as demonstrated by the inh ibitory effect of pharmacological PI3K blockers or overexpression of a domi nant negative Akt construct. Similarly, the potent angiogenic growth factor VEGF requires Akt to augment EPC numbers, suggesting an essential role for Akt in regulating hematopoietic progenitor cell differentiation. Given tha t statins are at least as potent as VEGF in increasing EPC differentiation, augmentation of circulating EPC might importantly contribute to the well-e stablished beneficial effects of statins in patients with coronary artery d isease.