Co-transfection of PDGF-B antisense oligonucleotide and tissue-type plasminogen activator gene prevents vascular anastomotic restenosis after coronary bypass

AIM: To elucidate the co-transfection of platelet derived growth factor B(PDGF-B) antisense oligonucleotide and tissue-type plasminogen activator gene to prevent vascular anastomotic restenosis after coronary bypass.METHODS: A dog model of vascular anastomotic restenosis after coronary bypass was constructed.A constructed tissue-type plasminogen activator(tPA) gene plasmid and a designed PDGF-B oligonucleotide were used to transfect into the dog cardiomyocytes and anastomotic vascular smooth muscle cells(VSMCs) at the same time of coronary bypass,using a therapeutic ultrasound for the gene delivery.Effects of these two genes on thrombosis in local anastomotic vessels,the expressions of proliferating cell nuclear antigen(PCNA) and PDGF-B mRNA by VSMCs and the proliferation of vascular intima were observed with the methods of routine pathological,immuno-histochemical staining,in situ hybridization and morphometry.RESULTS: PDGF-B antisense oligonucleotide and tissue-type plasminogen activator gene were succesfully transfected.These two genes significantly inhibited the expressions of PCNA and PDGF-B mRNA in intimal VSMCs with the inhibitory rates of 65.01% and 81.75%,respectively.The local intimal thickness and area also reduce markablely and the thrombosis of the anastomosis was prevented followed by the reduction of the anastomotic restenotic rate of 62.63%.CONCLUSION: Co-transfection of PDGF-B antisense oligonucleotide and tissue-type plasminogen activator gene inhibits the dog experimental anastomotic restenosis after coronary bypass.