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| The Role of Vascular Endothelial Growth Factor and Signal Transducer and Activator of Transcription 3 Activity in the Enhanced In-Stent Restenosis by Granulocyte-Colony Stimulating Factor in Bare and Drug-Eluting Stents |
| 전남대학교병원 순환기내과 |
| 안영근, 김용숙, 임상엽, 정명호, 주수연, 홍문화, 김정하, 이상록, 김계훈, 손일석, 홍영준, 박형욱, 김주한, 김원, 조정관, 박종춘, 강정채 |
Background: Using Granulocyte-Colony Stimulating Factor (G-CSF) itself and to mobilize stem cells has shown promise in infarcted heart. But, with use of G-CSF, aggravation of in-stent restenosis (ISR) may occur and aggressive strategy to prevent ISR is needed. The purpose of this study was to elucidate the mechanism of enhanced ISR by G-CSF in porcine model. Methods: Porcine aorta smooth muscle cells (PASMC) were used in vitro assay. Twenty bare stents (3*18 mm) were implanted in 20 porcine coronary arteries (Stents without G-CSF: Group I, Stents with G-CSF: Group II, n=10 in each group). G-CSF (10 µg/kg/day, once a day) was injected subcutaneously for 7 days from 24 hour after stent implantation. The implantation of Cypher stents is ongoing be performed. Twenty eight days after stenting, quantitative coronary angiography, intravascular ultrasound, and histomorphometric analysis were performed. The growth rates of G-CSF-treated PASMC were determined by MTT assay for three days. Immunohistochemical analysis and western blot were performed by using Signal Transducer and Activator of Transcription (STAT)-3, Akt, and vascular endothelial growth factor (VEGF) antibodies. Results: In porcine stented coronary arteries, area stenosis was 27.9±9.6 % in Group I and 76.7±12.0 % in Group II at 28 days (p<0.001). The ratio of inflammatory cells out of the number of total cells in the neointima was 6.5±1.7 % in Group I and 10.1±6.3 % in Group II at 28 days (p<0.001). STAT-3, phosphorylated STAT-3, and VEGF were over-expressed in neointima from group II compared with those from group I. The expression of phosphorylated Akt was not different between two groups. In G-CSF (100 ng/mL) treated PASMC, STAT-3 was phosphorylated in 1 hour and sustained for 48 hours, whereas expressions of VEGF and phosphorylated Akt were not changed during G-CSF treatment. Cellular growth rate was accelerated by G-CSF (120% vs. control, p=0.038) in three days. Conclusion: The VEGF and STAT-3 are important role in development of enhanced ISR by G-CSF. The results of Cypher stents will be presented in Autumn meeting.
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