The impact of the capability of circulating progenitor cell to differentiate on myocardial salvage in patients with primary acute myocardial infarction.
BACKGROUND
Circulating endothelial progenitor cells (EPCs) are known to be involved in vasculogenesis and mobilized after acute myocardial infarction (AMI). To test the hypothesis that the angiogenic function of EPCs affects post-myocardial infarction (MI) myocardial salvage, we evaluated the number and potential differentiation of EPCs and compared these data with clinical parameters 6 months after MI.


RESULTS
Consecutive 51 patients (age, 61+/-8 years, mean+/-SD) with primary AMI who were successfully treated with stenting were enrolled. EPC identified as CD45low, CD34+, CD133+, and VEGFR2+ was quantified by a flow cytometry. The potential of EPCs to differentiate into endothelial cells (EPC differentiation) was also confirmed by the upregulation of CD31 and VEGFR2 after 7 days of culture. According to the proportion of EPC fraction, patients were divided into 2 groups (cut-off value=median). Although no difference was seen in myocardial damage shown by mean peak CK leakage and mean area at risk between the differentiated group (n=26) and nondifferentiated group (n=25), the number of attached cell was greater in differentiated group than in the nondifferentiated group (P=0.023). Left ventricular function and ischemic damaged area were assessed by scintigraphic images of (123)I-BMIPP in the acute phase and (99m)Tc-tetrofosmin in the chronic phase. We found that a greater increase in myocardial salvage (P=0.0091), decrease in end-systolic volume (P=0.012), and recovery of ejection fraction (P=0.011) occurred in the group with differentiated EPCs than in the nondifferentiated group.


CONCLUSIONS
In patients with primary AMI, the capability of EPCs to differentiate influences the functional improvement and infarct size reduction, indicating that manipulation of EPCs could be a novel therapeutic target to salvage ischemic damage.
Numaguchi
Yasushi
Y
Nagoya University Graduate School of Medicine, Department of Cardiology, 65 Tsurumai, Showa, Nagoya 466-8550. Japan. numa2@med.nagoya-u.ac.jp
Sone
Takahito
T
Okumura
Kenji
K
Ishii
Masakazu
M
Morita
Yasuhiro
Y
Kubota
Ryuji
R
Yokouchi
Kazuhiko
K
Imai
Hajime
H
Harada
Mitsunori
M
Osanai
Hiroyuki
H
Kondo
Takahisa
T
Murohara
Toyoaki
T
D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D015415:Biomarkers; D002454:Cell Differentiation; D042783:Endothelial Cells / Q000166:cytology*; D004730:Endothelium, Vascular / Q000166:cytology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D008875:Middle Aged; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology / Q000601:surgery* / Q000628:therapy; D009206:Myocardium / Q000473:pathology; D018919:Neovascularization, Physiologic; D015607:Stents; D013318:Stroke Volume; D015899:Tomography, Emission-Computed, Single-Photon; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling
D015415:Biomarkers