Effect Of Co-transfection Of VEGF And PCNA-ASODN On Restenosis In Rabbits After Percutaneous Transluminal Coronary Angioplasty

Objectives To explore the effect of co-transfection of vascular endothelial growth factor (VEGF) and proliferating cell nuclear antigen antisense oligodeoxy-nucleotides (PCNA-ASODN) on restenosis after percutaneous transluminal coronary angioplasty.Methods 32 healthy Zelanian rabbits were randomly divided into four groups: the control group, the VEGF group, the PCNA-ASODN group, and the (VEGF+ PCNA-ASODN) group. Using pluronic gel as the control-released carrier,300μg VEGF or PCNA-ASODN were given to the adventitia of femoral iliac artery which became restenosis after balloon injury in rabbits.4 weeks later, the intima, middle structure and local thrombosis of the injured vascular specimen were observed by optical microscope, the neointimal endothelial cells, intima and media were examined by electronic microscope, and then the ratios of intima/media (I/M) area and the ratios of I/M thickness were figured out. mRNA expression of VEGF and PCNA were measured by reverse transcription-PCR. Protein expression of VEGF and PCNA were examined with immunohistochemistry.Results In the control group, the vascular endothelial were mostly lost under the optical microscope, the intima were hyperplasia notably, especially in the part of no vascular endothelial, and the proliferation of smooth cells in the media were irregularly. But in the VEGF group and PCNA-ASODN group, the vascular endothelial were repaired partly, the intima were less hyperplasia, and the smooth cells in the media were mild hyperplasia. While in the co-transfection group, the vascular endothelial were integrity and smooth, the proliferation of intima were gently, and there weren't obvious changes in adventitia. Measured by electronic microscope, the ratios of intima/media (I/M) area and thickness in the VEGF group and PCNA-ASODN group were significantly lower than the control group (P<0.01), especially in the PCNA-ASODN group (P<0.01); While in the co-transfection group, the ratios were much lower than that in the VEGF group (P<0.01) and PCNA-ASODN group (P<0.01). The mRNA expression of VEGF increased higher in the VEGF group (P<0.01) and co-transfection group than the other groups (P<0.01), but there was no significant difference between themselves; The mRNA expression of PCNA in the PCNA-ASODN group and co-transfection group were much lower than other groups (P<0.01), but there was also no significant different between themselves. The same results were seen in protein expression of VEGF and PCNA by immune-histochemistry.Conclusion Co-transfection of VEGF and PCNA-ASODN could inhibit the neointimal hyperplasia and restenosis more effectively.