Gene Transfer of Calcitonin Gene–Related Peptide Suppresses Development of Allograft Vasculopathy

Abstract

To explore suppression of allograft vasculopathy by transfer of the calcitonin gene-related peptide (CGRP). The descending thoracic aortas from Lewis rats were grafted to the abdominal aortas of F344 rats, and the rats were randomized into 2 groups. A gene construct containing sequences from the adenoviral oncoprotein, the CGRP, and the enhanced green fluorescent protein was transferred into 1 group, and the sequences for the adenoviral oncoprotein and enhanced green fluorescent protein were transferred into a control group. Specimens were harvested at 4 and 8 weeks. Gene transfer was confirmed at fluorescence microscopy of frozen tissue sections, and expression was measured using reverse transcriptase-polymerase chain reaction. We determined the locations and levels of vascular cell adhesion molecule-1 (VCAM-1) and inducible nitric oxide synthase (iNOS) at immunohistochemistry and measured apoptosis. The CGRP gene was expressed only in the CGRP group at 4 weeks. The vascular luminal occlusion score in the CGRP group was lower than in the control group. The apoptotic index of the CGRP group was lower than in the control group only at 4 weeks. The VCAM-1 immunohistochemistry score in the CGRP group was lower than in the control group; however, the iNOS immunohistochemistry score in the CGRP group was lower than in the control group in the intima only at 4 weeks. The expression of CGRP effectively suppressed the development of allograft vasculopathy and encroachment by lymphocytes and inflammatory cells. This reduced the levels of VCAM-1 to inhibit apoptosis induced by iNOS; thus, the tissue of the allografted vessel was protected and rejection was averted.