Abstract 9409: Aging Inhibits Angiogenic Response in a Rat Model of Hindlimb Ischemia: A HUR-VEGF Dependent Mechanism

Introduction: Human antigen R (HUR) is a RNA stablilizer and its expression decressed in aging organism, however, its downstream signal pathways remain modest clarified. Here, we examined whether HUR plays a role in angiogenic response using an aging rat model of hindlimb ischemia. Methods and Results: Male Sprague-Dawley rats were divided into 2 groups: the young group (12 week-old) and the aging group (96 week-old). The left femoral artery of all rats were excised, and the extent of angiogenesis and collateral vessels in the ischemic limb were examined for 2 weeks. At postoperative day 14, aging rats exhibited impaired angiogenic action (skin temperature, capillary density and angiography) and decreased angiogenic factor expressions (vascular endothelial growth factor [VEGF], hypoxic inducible factor-1α and nitric oxide [NO]) in ischemic muscles. The protein expression of HUR as well as endothelial nitric oxide synthetase (eNOS) phosphorylation were significantly inhibited in aging rats as well. In vitro, we applied anti-HUR small interfering RNA to transfect human umbilical vein endothelial cells (HUVECs). The results showed that transfected HUVECs exhibited decreased the capacities of VEGF/NO production, tube formation and apoptotic resistence compared with control. Conclusions: Our results domenstrated that the down-regulation of HUR plays a key role in aging-related poor angiogenic response.