Mobilization of endothelial progenitor cells in patients with acute myocardial infarction

Background - Endothetial progenitor cells (EPCs) circulate in adult periphe ral blood (PB) and contribute to neovascularization. However, little is kno wn regarding whether EPCs and their putative precursor, CD34-positive monon uclear cells (MNCCD34+),, mobilized into PB in acute ischemic events in hum ans. Methods and Results - Flow cytometry revealed that circulating MNCCD34+ cou nts significantly increased in patients with acute myocardial infarction (n =16), peaking on day 7 after onset, whereas they were unchanged in control subjects (n=8) who had no evidence of cardiac ischemia. During culture, PB- MNCs formed multiple cell clusters, and EPC-like attaching cells with endot helial cell lineage markers (CD31, vascular endothelial cadherin, and kinas e insert domain receptor) sprouted from clusters. In patients with acute my ocardial infarction, more cell clusters and EPCs developed from cultured PB -MNCs obtained on day 7 than those on day 1. Plasma levels of vascular endo thelial growth factor significantly increased, peaking on day 7, and they p ositively correlated with circulating MNCCD34+ counts (r=0.35, P=0.01). Conclusions - This is the first clinical demonstration showing that lineage -committed EPCs and MNCCD34+, their putative precursors, are mobilized duri ng an acute ischemic event in humans.