Mobilization of endothelial progenitor cells in patients with acute myocardial infarction

Background - Endothetial progenitor cells (EPCs) circulate in adult peripheral blood (PB) and contribute to neovascularization. However, little is known regarding whether EPCs and their putative precursor, CD34-positive mononuclear cells (MNCCD34+),, mobilized into PB in acute ischemic events in humans. Methods and Results - Flow cytometry revealed that circulating MNCCD34+ counts 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 endothelial cell lineage markers (CD31, vascular endothelial cadherin, and kinase insert domain receptor) sprouted from clusters. In patients with acute myocardial infarction, more cell clusters and EPCs developed from cultured PB-MNCs obtained on day 7 than those on day 1. Plasma levels of vascular endothelial growth factor significantly increased, peaking on day 7, and they positively 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 during an acute ischemic event in humans.