Long term evaluation of coronary bypass with vein grafts transfered with CNP gene

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C-type natriuretic peptide (CNP) acts toward relaxation and growth inhibition of vascular smooth muscle cells (VSMC) via activation of selective receptor, ANP-B receptor. We have developed a replication deficient adenoviral vector overexpressing CNP gene (Ad.CNP), and reported that this vector potently inhibits proliferation of cultured VSMC. In this study, using balloon injury model of rabbit carotid artery, we revealed that topical overexpression of CNP gene after injury markedly inhibits neointimal proliferation after endothelial injury in vivo. Moreover, redifferentiation of VSMC and regeneration of endothelial cells were observed in the neointima treated with Ad.CNP. We then examined effects of CNP overexpression on autologous vein grafts. Rabbit jugular vein treated with Ad.CNP or control vector ex vivo were interposed into carotid artery. In veins treated with Ad.CNP, tissue concentration of CNP and cGMP were elevated and inhibition of neointimal thickening, inhibition of early and late thrombosis and promotion of endothelial regeneration were observed. Based on these findings, we tried to develop coronary bypass graft model using internal mammary artery and hind limb vein of beagle. However, mainly because of technical difficulties, we failed to establish the model to evaluate long-term evaluation of the grafts.