Effects of adenovirus-mediated transfer of C-type natriuretic peptide gene on arterialized vein graft.

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We previously reported that C-type natriuretic peptide (CNP) occurs in vascular endothelial cells and acts toward relaxation and growth inhibition of smooth muscle cell. The aim of this study was to overexpress CNP by adenovirus-mediated gene transfer in proliferative vascular lesions and investigate its effects on vascular remodeling in vivo. Replication-deficient adenoviral vectors encoding CNP gene (Ad.CNP) and E.coli LacZ gene (Ad.LacZ) were developed by conventional method.1. After the femoral artery of male Japanese White rabbits was injured by balloon catheter, Ad.CNP or Ad.LacZ was instilled in the vascular lumen for 30 minutes. Two weeks later, neointimal formation after balloon injury was significantly suppressed in CNP group compared with LacZ group. In CNP group, CNP staining was more intense than in LacZ group and expression of SM-2, which is the molecular marker of well-differentiated SMCs, was induced in the residual neointima. Angiotensin II caused more potent vasoconstriction in CNP group than in LacZ group. Evans blue dye staining revealed accelerated reendothelialization in CNP group and acetylcholine caused more potent relaxation in CNP group than in LacZ group.2. Autologous rabbit jugular vein grafts were incubated ex vivo in a solution of Ad.CNP or Ad.LacZ and then interposed in the carotid artery. Reendothelialization, mural thrombi formation, and intima/media ratio were evaluated on the 14th and 28th postoperative days. More reendothelialization was seen in Ad.CNP-infected grafts than in Ad.LacZ-infected grafts. The mural thrombus area was smaller in Ad.CNP group than in Ad.LacZ group. Neointimal thickening was significantly suppressed in the Ad.CNP group.