Mobilization of endothelial progenitor cells in patients with acute myocardial infarction

• Published in: Circulation (New York, N.Y.) N.Y.), 2001-06, Vol.103 (23), p.2776-2779
• Main Authors: SHINTANI, Satoshi, MUROHARA, Toyoaki, IKEDA, Hisao, UENO, Takafumi, HONMA, Tomoki, KATOH, Atsushi, SASAKI, Ken-Ichiro, SHIMADA, Toshifumi, OIKE, Yuichi, IMAIZUMI, Tsutomu
• Format: Article
• Language: English
• Subjects: Aged; Antigens, CD; Antigens, CD34 - metabolism; Antigens, Differentiation - blood; Antigens, Differentiation - metabolism; Biological and medical sciences; Cadherins - metabolism; Cardiology. Vascular system; Cell Count; Cell Lineage; Cells, Cultured; Coronary heart disease; Creatine Kinase - blood; Cytokines - blood; Endothelial Growth Factors - blood; Endothelium, Vascular - pathology; Female; Flow Cytometry; Heart; Humans; Leukocytes, Mononuclear - cytology; Leukocytes, Mononuclear - metabolism; Lymphokines - blood; Male; Medical sciences; Middle Aged; Myocardial Infarction - blood; Myocardial Infarction - pathology; Neovascularization, Physiologic; Platelet Endothelial Cell Adhesion Molecule-1 - metabolism; Stem Cells - cytology; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/hc2301.092122

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. 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). 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.