Outside stenting of the vein graft decreases VEGF-A expression and induces significant down-regulation of VEGFR-1 in the intimal and medial layers after the re-endothelialization period
Michal Krejca, Andrzej Plewka, Przemyslaw Szmagala, Danuta Plewka, Grazyna Nowaczyk, Janusz Skarysz, Krzysztof Bialek, Michal Guc, Andrzej Bochenek
Med Sci Monit 2010; 16(3): BR89-96
Available online: 2010-02-26
Neointimal hyperplasia (NIH) in vein grafts implanted into the arterial system develops after re-endothelialization and is considered a significant risk factor of occlusion. Evidence suggests that VEGF-A expression with VEGFR-2 activation and/or VEGFR-1 down-regulation might be involved in inhibiting NIH formation. The aim was to assess whether a stented vein graft (SV) has an impact on VEGF-A and VEGFR-1 expression compared with non-stented vein grafts.
Material and Method: Twelve sheep received a radial vein with an outside stent (SV) and a radial vein (RV) transplanted into their carotid arteries. The covering of the luminal surface of the SV and RV grafts by endothelium was 98.3% and 96.3%, respectively, at 6 weeks. From the 6th to 12th weeks after transplantation, the time course of total VEGF-A expression and VEGFR-1 expression were evaluated separately for the intima and media.
Results: VEGF-A and VEGFR-1 expression were significantly lower in the SV than in the RV group in the intima. In the media the SV grafts were associated with higher VEGF-A and VEGFR-1 expression at 6 and 8 weeks, but lower values were observed at weeks 10 and 12 compared with the RV grafts. Comparing the time courses of VEGF-A and VEGFR-1 expression in the intima and media with intimal/medial thickening in the SV and RV groups, negative correlations for the SV grafts were found.
Conclusions: These findings indicate that outside stenting of the vein graft decreases VEGF-A expression and induces significant down-regulation of VEGFR-1 in the intima and media after the re-endothelialization.
Keywords: Vascular Endothelial Growth Factor A - metabolism, Tunica Media - pathology, Tunica Intima - pathology, Time Factors, Stents, Sheep, Endothelium, Vascular - pathology, Down-Regulation, Cell Proliferation, Blood Vessel Prosthesis, Animals, Vascular Endothelial Growth Factor Receptor-1 - metabolism, Veins - pathology