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Enhanced mobilization of CD34(+) progenitor cells expressing cell adhesion molecules in patients with STEMI
Michael Brehm1, Petra Ebner, Frauke Picard
1Division of Cardiology, Pneumology and Angiology, Department of Medicine, Heinrich-Heine University of Düsseldorf, Düsseldorf, Germany. brehm@med.uni-duesseldorf.de
Insights
Patients with ST-segment elevation myocardial infarction (STEMI) show increased mobilization of CD34+ progenitor cells expressing adhesion molecules compared to coronary artery disease (CAD) patients. This suggests enhanced cell migration for potential myocardial repair.
Area of Science:
- Cardiovascular Research
- Stem Cell Biology
- Regenerative Medicine
Background:
- Adult stem cells play a role in myocardial regeneration following ischemic injury.
- Understanding stem cell mobilization is crucial for developing cardiac repair strategies.
Purpose of the Study:
- To quantify mobilized CD34+ progenitor cells (CD34+/CD117+, CD34+/KDR+) in peripheral blood relative to cytokines.
- To assess circulating CD34+ cells expressing cell adhesion molecules (CAM) in STEMI vs. CAD patients.
Main Methods:
- Flow cytometry was used to quantify stem cells and adhesion molecule expression.
- ELISA determined levels of inflammatory cytokines (IL-6, G-CSF, VEGF) and chemokines (SDF-1, HGF).
- Study included 23 STEMI patients, 24 CAD patients, and 15 controls, matched for age and cardiac function.
Main Results:
- STEMI patients exhibited significantly higher levels of circulating CD34+/CD117+ and CD34+/KDR+ progenitor cells compared to CAD patients.
- Mobilization of CD34+ progenitor cells expressing CXCR4, LFA-1, VLA-4, and ICAM-1 was significantly higher in STEMI patients versus CAD patients.
- Upregulated G-CSF, IL-6, and HGF cytokines were observed in STEMI patients compared to controls and CAD patients.
Conclusions:
- STEMI patients demonstrate increased mobilization of CD34+ progenitor cells, including CD34+/CD117+ and CD34+/KDR+ phenotypes, relative to CAD patients.
- Enhanced expression of cell adhesion molecules on CD34+ progenitor cells was observed in STEMI patients.
- Increased adhesion molecule expression may facilitate progenitor cell transmigration and implantation into ischemic myocardium, promoting myocardial repair.
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).
Materials And 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.
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