Adenoviral-mediated uteroglobin gene transfer inhibits neointimal hyperplasia after balloon injury in the rat carotid artery

Objective: Uteroglobin is a protein with potent anti-inflammatory and immun omodulatory effects. We hypothesize that induction of uteroglobin expressio n in the artery wall by local adenoviral gene transfer will decrease neoint imal hyperplasia in the rat carotid artery after balloon injury. Methods: Seven male Sprague-Dawley rats underwent balloon injury of the com mon carotid artery. After the injury, with flow occluded, the artery was in stilled with 50 muL of the adenoviral vector encoding uteroglobin gene (Ad. UG) at a concentration of 1.35 x 10(11) pfu/mL (n = 7) or 0.68 x 1011 pfu/m l (n = 7) (n = 7), Control animals were similarly treated: either an adenov irus encoding for beta -galactosidase gene (Ad.LacZ) at 1 x 10(11) pfu/mL, (n = 7) or the phosphate-buffered saline (PBS) vehicle (n = 6) was used. Th e solution was allowed to dwell for 20 minutes. The rats were humanely kill ed after 14 days by perfusion fixation, and the carotid arteries were secti oned for analysis with computerized planimetry. The intima-media area ratio s were calculated for each artery and compared with analysis of variance wi th Bonferroni/Dunn post hoc testing. One additional rat from the PBS, Ad.La cZ, and Ad.UG (1.35 x 1011 pfu/mL) groups was humanely killed 4 days after treatment for carotid artery protein extraction and Western blotting. Results: Uteroglobin protein production was confirmed in the Ad.UG-treated arteries with Western blotting. Morphometric analysis showed that the Ad.UG group at 1.35 x 1011 pfu/ml had a significantly lower intima-media area ra tio than both the Ad.LacZ (P = .002) and PBS (P = .004) controls. The Ad.UG group at 0.68 x 1011 pfu/ml was also significantly different from the Ad.L acZ (P = .003) and PBS (P = .006) controls. There was no statistical differ ence between the two control groups or between the two Ad.UG groups. Conclusion: Adenoviral gene transfer of uteroglobin, delivered intraluminal ly after arterial injury causes the production of uteroglobin protein and h as an inhibitory effect on neointimal accumulation in the rat model.