The effects of granulocyte-colony stimulating factor in bare stent and sirolimus-eluting stent in pigs following myocardial infarction

Sang Yeob Lim, Yong Sook Kim, Youngkeun Ahn, Myung Ho Jeong, Lee Sang Rok, Ju Han Kim, Key Hun Kim, Hyung Wook Park, Weon Kim, Jeong Gwan Cho, Jong Chun Park, Peter M. Kang, Robert S. Schwartz, Jung Chaee Kang

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Abstract

Objectives: The purpose of this study was to compare the effects of granulocyte-colony stimulating factor (G-CSF) on in-stent restenosis (ISR) in bare and sirolimus-eluting stents (SES) in a porcine myocardial infarction model. Background: Using G-CSF to mobilize stem cells has shown promise in infarcted heart. However, G-CSF may aggravate ISR and an aggressive strategy to prevent ISR is needed. Methods: Bare stents and SES were implanted in coronary arteries (Group I, bare stents; Group II, bare stents with G-CSF; Group III, SES; Group IV, SES with G-CSF, n = 10 in each group) 72 h after experimental myocardial infarction (MI). G-CSF (10 μg/kg/day) was injected for 7 days from 24 h after stent implantation. Results: In coronary angiographic and histomorphometric analysis, percent area stenosis was significantly increased in Group II compared with that in Group I at 28 days (P < 0.05). The ratio of inflammatory cells in the neointima was higher in Group II (P < 0.05). No significant differences were observed between Group III and IV. In Group II, phosphorylated signal transducers and activators of transcription (STAT)-3, STAT-3, and vascular endothelial growth factor (VEGF) showed increased neointimal expression. In porcine aortic smooth muscle cells (PASMC), G-CSF increased the growth rate, migration, STAT-3 phosphorylation, and VEGF, which were suppressed by rapamycin and AG490, a STAT-3 inhibitor. Conclusions: STAT-3 and VEGF are important in the development of enhanced ISR by G-CSF in bare stents. SES could be a good strategy to prevent the G-CSF-stimulated proliferation and migration of smooth muscle cells, which could be responsible for neointimal hyperplasia.

Original languageEnglish
Pages (from-to)304-311
Number of pages8
JournalInternational Journal of Cardiology
Volume118
Issue number3
DOIs
Publication statusPublished - 2007 Jun 12
Externally publishedYes

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Keywords

  • Bare stent
  • Granulocyte-colony stimulating factor
  • In-stent restenosis
  • Sirolimus-eluting stent

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Lim, S. Y., Kim, Y. S., Ahn, Y., Jeong, M. H., Rok, L. S., Kim, J. H., Kim, K. H., Park, H. W., Kim, W., Cho, J. G., Park, J. C., Kang, P. M., Schwartz, R. S., & Kang, J. C. (2007). The effects of granulocyte-colony stimulating factor in bare stent and sirolimus-eluting stent in pigs following myocardial infarction. International Journal of Cardiology, 118(3), 304-311. https://doi.org/10.1016/j.ijcard.2006.07.018