Aims: 棺-catenin has been known to be a transcriptional regulator of several genes that are involved in proliferation and survival. But little is known about a role for 棺-catenin in endothelial cell proliferation. We investigated the potential of 棺-catenin for therapeutic neovascularization, using adenoviral gene transfer in a mouse hindlimb ischemia model. Methods: To impair angiogenesis in response to hindlimb ischemia, mouse were fed with 2% high-cholesterol diet. After 2 weeks of the dietary intervention, unilateral limb ischemia was surgically induced in all animals. Adenovirus containing either wild type(WT) 棺-catenin(n=8) or constitutively-active quadruple mutant(QM) 棺-catenin(n=8) or GFP gene(n=8) were injected into the adductor muscle immediately after femoral artery removal(1��10⁹ pfu per mouse, total 40ul divided into 4 sites). To identify a characteristic gene expression profile after 棺-catenin gene transfer, RT-PCR and Western blot analysis were performed. Results: Throughout the course of the experiment, 棺-catenin protein was detected by immunostaining of hindlimb where gene was delivered. Laser Doppler blood flow analyses showed significant increase in the blood flow ratio of ischemic/ normal limb in the 棺-catenin group(WT & QM) compared with GFP controls(GFP: WT: QM= 0.70짹0.03: 0.93짹0.05: 0.96짹0.06, p<0.05) at 2 weeks after surgery. Histologic evaluation by anti-CD-31 immunostaining showed a statistically significant increase of capillary density(per mm²) in 棺-catenin group (increase of 2.88 fold in QM & 2.35 fold in WT compared with GFP controls). RT-PCR and western blot results in 棺-catenin group showed significant increase of heparansulfate proteoglycan and cyclin E, both of which are downstream target gene of 棺-catenin, compared with GFP gene transfer control. Conclusion: Adeno-棺-catenin gene delivery promotes angiogenesis after hindlimb ischemia. The effect of 棺-catenin on endothelial cell may be modulation of cell cycle regulation and proliferation. Furthermore, adenovirus-mediated 棺-catenin gene transfer is considered as a promising genetic modification to improve endothelial function and proliferation.