Enhanced mobilization of CD34(+) progenitor cells expressing cell adhesion molecules in patients with STEMI.
BACKGROUND
Adult stem cells can contribute to myocardial regeneration after ischemic injury. The aim of the study was to determine (1) the amount of mobilized CD34(+)/CD117(+), CD34(+)/KDR(+) cells into peripheral blood (PB) in relation to inflammatory and haematopoietic cytokines, (2) the presence of circulating CD34(+) cells, expressing cell adhesion molecules (CAM), in patients with ST-segment elevation myocardial infarction (STEMI) in comparison to patients with coronary artery disease (CAD).


METHODS
Twenty-three patients with STEMI (<12 h), 24 patients with CAD and 15 control subjects were enrolled in this study. The patients were matched in age, 2-CAD, ejection fraction (45%) and end-diastolic volume index (70 ml/m(2)). The number of stem cells and the expression of adhesion molecules were quantified by use of flow cytometry. Inflammatory cytokines [interleukin-6 (IL-6), granulocyte colony-stimulating factor (G-CSF), vascular endothelial growth factor] and chemotactic factors as stromal cell-derived factor-1 (SDF-1), hepatocyte growth factor (HGF) were determined by ELISA.


RESULTS
The amount of circulating progenitor cells including CD34(+)/CD117(+) and CD34(+)/KDR(+) cells was significantly higher in patients with STEMI than in patients with CAD (CD34(+)/CD117(+) 433 +/- 128 vs. 100 +/- 17, P = 0.012; CD34(+)/KDR(+) 253 +/- 41 vs. 128 +/- 24, P = 0.02). The mobilization of CD34(+) progenitor cells expressing CXCR4-receptor, lymphocyte function-associated antigen-1 (LFA-1), very late antigen-4 (VLA-4) and ICAM-1 into PB was significantly higher in patients with STEMI compared to CAD (CD34(+)/CXCR4(+) 740 +/- 327 vs. 136 +/- 23, P = 0.006; CD34(+)/LFA-1 976 +/- 227 vs. 329 +/- 41, P = 0.025; CD34(+)/VLA4(+) 830 +/- 161 vs. 330 +/- 31, P = 0.007; CD34(+)/ICAM(+) 387 +/- 66 vs. 144 +/- 26, P < 0.001). Additionally, the cytokines G-CFS, IL-6 and HGF were upregulated and significantly increase in the STEMI group compared with controls and CAD (G-CSF 50.6 +/- 6.8 vs. 23 +/- 3 vs. 23.8 +/- 2, P (Co vs. STEMI) < 0.001, P (Co vs. CAD) = n.s., P (STEMI vs. CAD) < 0.001; IL-6 8.4 +/- 0.6 vs. 3.8 +/- 1.9 vs. 2.6 +/- 1, P (Co vs. STEMI) < 0.001, P (Co vs. CAD) = n.s., P (STEMI vs. CAD) < 0.001; HGF 4,502 +/- 461 vs. 686 +/- 195 vs. 1,746 +/- 461, P (Co vs. STEMI) < 0.001, P (Co vs. CAD) = n.s., P (STEMI vs. CAD) < 0.001), while the level of SDF-1 was increased in patients with CAD compared to controls and patients with STEMI (3,035 +/- 286 vs. 2,028 +/- 76 vs. 2,154 +/- 234, P (Co vs. STEMI) = n.s., P (Co vs. CAD) = n.s., P (STEMI vs. CAD) = 0.005).


CONCLUSIONS
The study demonstrates in patients with STEMI an increased mobilization of progenitor cells like CD34(+)/CD117(+) and CD34(+)/KDR(+) compared to CAD. Furthermore, we could shown that in patients with STEMI the mobilization of CD34(+) progenitor cells with expressed CAM was increased. It is to speculate that an enhanced expression of adhesion molecules may increase the transmigration and implantation of progenitor cells into ischemic myocardium for myocardial repair.
Brehm
Michael
M
Division of Cardiology, Pneumology and Angiology, Department of Medicine, Heinrich-Heine University of Düsseldorf, Düsseldorf, Germany. brehm@med.uni-duesseldorf.de
Ebner
Petra
P
Picard
Frauke
F
Urbien
Ryan
R
Turan
Gökmen
G
Strauer
Bodo-Eckehard
BE
D018952:Antigens, CD34 / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002465:Cell Movement; D002478:Cells, Cultured; D003324:Coronary Artery Disease / Q000378:metabolism / Q000473:pathology*; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology*
D018952:Antigens, CD34; D015815:Cell Adhesion Molecules; D016207:Cytokines