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

Abstract

Objective: Uteroglobin is a protein with potent anti-inflammatory and immunomodulatory effects. We hypothesize that induction of uteroglobin expression in the artery wall by local adenoviral gene transfer will decrease neointimal hyperplasia in the rat carotid artery after balloon injury. Methods: Seven male Sprague-Dawley rats underwent balloon injury of the common carotid artery. After the injury, with flow occluded, the artery was instilled with 50 μL of the adenoviral vector encoding uteroglobin gene (Ad.UG) at a concentration of 1.35 × 1011 pfu/mL (n = 7) or 0.68 × 1011 pfu/mL (n = 7) (n = 7). Control animals were similarly treated: either an adenovirus encoding for β-galactosidase gene (Ad.LacZ) at 1 × 1011 pfu/mL (n = 7) or the phosphate-buffered saline (PBS) vehicle (n = 6) was used. The solution was allowed to dwell for 20 minutes. The rats were humanely killed after 14 days by perfusion fixation, and the carotid arteries were sectioned for analysis with computerized planimetry. The intima-media area ratios were calculated for each artery and compared with analysis of variance with Bonferroni/Dunn post hoc testing. One additional rat from the PBS, Ad.LacZ, and Ad.UG (1.35 × 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 × 1011 pfu/mL had a significantly lower intima-media area ratio than both the Ad.LacZ (P =.002) and PBS (P =.004) controls. The Ad.UG group at 0.68 × 1011 pfu/mL was also significantly different from the Ad.LacZ (P =.003) and PBS (P =.006) controls. There was no statistical difference between the two control groups or between the two Ad.UG groups. Conclusion: Adenoviral gene transfer of uteroglobin, delivered intraluminally after arterial injury causes the production of uteroglobin protein and has an inhibitory effect on neointimal accumulation in the rat model. (J Vasc Surg 2000;32:1111-7.)