Mobilization of CD34+ KDR+ endothelial progenitor cells predicts target lesion revascularization.
BACKGROUND
Endothelial lesion and regeneration are critical events in the process leading to in-stent restenosis (ISR) after bare metal stent (BMS) percutaneous coronary intervention (PCI).


OBJECTIVE
To prospectively investigate the relationship between biomarkers reflecting endothelial turnover and the occurrence of ISR.


METHODS
We performed a multicenter prospective observational study that included 156 patients undergoing elective PCI with BMS. Endothelial lesion was assessed by the enumeration of circulating endothelial cells (CECs). Endothelial regeneration was evaluated by enumeration of circulating CD34+ progenitor cells (CD34+ PCs) and CD34+ KDR+ endothelial progenitor cells (EPCs). Measurements were performed before PCI, and 6 and 24 h after PCI. Dynamic changes were evaluated by calculating the delta value of each marker. The primary and secondary endpoints of the study were clinical target lesion revascularizations (TLRs) and major adverse cardiovascular events (MACEs) after 6 months of follow-up.


RESULTS
During follow-up, 28 MACEs were recorded, including 27 TLRs. PCI induced a significant rise in the numbers of CECs, CD34+ PCs, and CD34+ KDR+ EPCs. Baseline, 6-h and 24-h levels of these markers did not differ between patients with and without TLR. The delta percentage of CD34+ KDR+ EPCs was significantly reduced in patients with TLR as compared with patients without TLR (- 0.56 ± 8.1 vs. 2.91 ± 6.2; P = 0.015). In multivariate analysis, the delta percentage of CD34+ KDR+ EPCs independently predicted the occurrence of TLR and MACEs (P = 0.02 and P = 0.014, respectively).


CONCLUSIONS
The endothelial regenerative response to injury induced by PCI, assessed by CD34+ KDR+ EPCs mobilized among progenitor cells, determines the risk of TLR and MACEs in stable coronary artery disease patients.
Département de cardiologie, Hôpital universitaire nord, Faculté de médecine, Aix Marseille Université, Marseille, France. laurentbonello@yahoo.fr
L
L
Bonello
K
K
Harhouri
K
K
Baumstarck
L
L
Arnaud
N
N
Lesavre
C
C
Piot
F
F
Paganelli
F
F
Dignat-George
F
F
Sabatier
D000368:Aged; D018952:Antigens, CD34 / Q000276:immunology*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013234:Stem Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D051193:Toll-Like Receptors / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
D018952:Antigens, CD34; D051193:Toll-Like Receptors; D040301:Vascular Endothelial Growth Factor Receptor-2