Gene Transfer of Calcitonin Gene-Related Peptide Inhibits Macrophages and Inflammatory Mediators in Vein Graft Disease

Vein graft disease is a chronic inflammatory disease and limits the late results of coronary revascularization. Calcitonin gene-related peptide (CGRP) inhibits macrophages infiltrated and inflammatory mediators, we hypothesized that transfected CGRP gene inhibits macrophages infiltrated and inflammatory mediators in vein graft disease. Autologous rabbit jugular vein grafts were incubated ex vivo in a solution of mosaic adeno-associated virus vectors containing CGRP gene (AAV2/1.CGRP) &x3001;escherichia coli lac Z gene (AAV2/1.LacZ) or saline and then interposed in the carotid artery. Intima/media ratio were evaluated at postoperative 4 weeks, Macrophages were marked with CD68 antibody by immunocytochemistry. Inflammatory mediators were mensurated with real-time PCR. Neointimal thickening was significantly suppressed in AAV2/1.CGRP group. Macrophages infiltrated and inflammatory mediators monocyte chemoattractant protein-1 (MCP-1)&x3001;tumor necrosis factor&x03B1;(TNF-&x03B1;)&x3001;inducible nitricoxide synthase (iNOS)&x3001;matrix metalloproteinase-9 (MMP-9) was significantly suppressed in AAV2/1.CGRP group.Gene transfected AAV2/1.CGRP suppressed neointimal hyperplasia in vein graft disease by suppressed macrophages infiltrated and inflammatory mediators.