Mobilization of Endothelial Progenitor Cells in Patients With Acute Myocardial Infarction

TLDR

Endothelial progenitor cells circulate in adult peripheral blood and contribute to neovascularization. The study aimed to determine whether EPCs and CD34‑positive mononuclear cells are mobilized into peripheral blood during acute ischemic events in humans. Flow cytometry showed that circulating CD34+ mononuclear cells rose sharply, peaking on day 7 after myocardial infarction onset, while cultured peripheral‑blood mononuclear cells formed clusters and sprouted EPC‑like cells expressing CD31, VE‑cadherin, and KDR. Patients with acute myocardial infarction exhibited higher circulating CD34+ counts, increased cluster and EPC formation from day 1 to day 7, and elevated VEGF levels that correlated with CD34+ counts, confirming mobilization of EPCs and their precursors during acute ischemia.

Abstract

Background —Endothelial 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 (MNC CD34+ ), are mobilized into PB in acute ischemic events in humans. Methods and Results —Flow cytometry revealed that circulating MNC CD34+ 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 MNC CD34+ counts ( r =0.35, P =0.01). Conclusions —This is the first clinical demonstration showing that lineage-committed EPCs and MNC CD34+ , their putative precursors, are mobilized during an acute ischemic event in humans.