Key result
Adenoviral uteroglobin gene transfer lowers intima-media area ratio versus controls in rat arterial injury.
Why the study?
Uteroglobin has potent anti-inflammatory and immunomodulatory effects, and its potential to decrease neointimal hyperplasia after arterial injury was investigated.
Does local adenoviral-mediated uteroglobin gene transfer reduce neointimal hyperplasia in male Sprague-Dawley rats after carotid artery balloon injury?
Does local adenoviral-mediated uteroglobin gene transfer reduce neointimal hyperplasia in male Sprague-Dawley rats after carotid artery balloon injury?
Adenoviral-mediated uteroglobin gene transfer effectively inhibits neointimal hyperplasia following arterial balloon injury in a rat model.
Answers are grounded in this paper and cite their sources.
Uteroglobin gene transfer attenuates neointimal hyperplasia in rats; hypothesis-generating for restenosis prevention, no clinical implications yet.
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 microL 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 10(11) pfu/mL (n = 7) (n = 7). Control animals were similarly treated: either an adenovirus 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. 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 x 10(11) 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 10(11) 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 x 10(11) 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.
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Larson et al. (2000) studied Neointimal hyperplasia after balloon injury (n=30). Adenoviral vector encoding uteroglobin gene (Ad.UG) vs. Adenovirus encoding beta-galactosidase (Ad.LacZ) or PBS vehicle was evaluated on Intima-media area ratio (p=0.002). Adenoviral gene transfer of uteroglobin lowered the intima-media area ratio compared to Ad.LacZ and PBS controls in a rat model of arterial injury.
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