Circulating endothelial progenitor cell levels and function in patients who experienced late coronary stent thrombosis.
OBJECTIVE
The pathogenesis of late coronary stent thrombosis may be related to impaired arterial healing. Endothelial progenitor cells (EPCs) have been shown to play an important role in repair and re-endothelialization following vascular injury. We hypothesized that patients who develop late stent thrombosis may have reduced or dysfunctional EPCs, and aimed to compare EPC level and function in patients who experienced stent thrombosis vs. matched controls.


RESULTS
Patients who developed late (> 30 days) stent thrombosis within the past 3 years were compared with matched patients who underwent stenting and did not develop stent thrombosis. All patients had blood samples taken ≥ 3 months from the stent thrombosis or index procedure. The proportion of peripheral mononuclear cells (PMNCs) expressing vascular endothelial growth factor receptor 2 (VEGFR-2), CD133, and CD34 was evaluated by flow cytometry. Endothelial progenitor cell colony forming units (CFUs) were grown from PMNCs, characterized and counted following 7 days of culture. The two groups (n = 30 each) were well-matched (93.3% men, mean age 60-62 years, 33.3% diabetes, 73-80% DESs). The proportion of cells co-expressing VEGFR-2, CD133, and CD34 was lower in the stent thrombosis group compared with the control [VEGFR-2(+)CD133(+): 0.18% (0.03-0.41%) vs. 0.47% (0.16-0.66%), P = 0.01; VEGFR-2(+)CD34(+): 0.32% (0.22-0.70%) vs. 0.66% (0.24-1.1%), P = 0.03]. The number of EPC CFUs was also lower in the stent thrombosis group [3.9% (3.2-5.5%) vs. 8.3% (6.5-13.4%) colonies/well, respectively, P < 0.0001].


CONCLUSIONS
Patients who suffered late coronary stent thrombosis appear to have reduced levels of circulating EPCs and impaired functional properties of the cells. These findings require validation by further studies, but may contribute to understanding the pathogenesis of late stent thrombosis.
Lev
Eli I
EI
Cardiology Department, Rabin Medical Center, Jabotinsky St, Petah-Tikva 49100, Israel. elil@clalit.org.il
Leshem-Lev
Dorit
D
Mager
Aviv
A
Vaknin-Assa
Hanna
H
Harel
Naama
N
Zimra
Yael
Y
Bental
Tamir
T
Greenberg
Gabi
G
Dvir
Dani
D
Solodky
Alejandro
A
Assali
Abid
A
Battler
Alexander
A
Kornowski
Ran
R
D015906:Angioplasty, Balloon, Coronary; D016022:Case-Control Studies; D023903:Coronary Restenosis / Q000097:blood / Q000473:pathology*; D042783:Endothelial Cells; D004730:Endothelium, Vascular / Q000473:pathology; D005260:Female; D006083:Graft Occlusion, Vascular / Q000473:pathology*; D006801:Humans; D007963:Leukocytes, Mononuclear; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000502:physiology; D013234:Stem Cells; D015607:Stents; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
D040301:Vascular Endothelial Growth Factor Receptor-2