Abstract Body: It has been reported that pharmacological inhibition of glycolysis attenuated abdominal aortic aneurysm (AAA) development in mice. Glucose transporters (GLUTs) incorporate glucose as a first step of glycolysis. GLUT1 over-expression in vascular smooth muscle cell (VSMC) appears to enhance atherosclerosis in a mouse model. In angiotensin II (AngII) plus BAPN model of mouse AAA, silencing of VSMC AngII type 1 rec receptors attenuated AAA development and rupture which was associated with less immune cell infiltration to the aortas. However, the role of VSMC GLUT1 in AAA remains elusive. Here we tested our hypothesis that VSMC GLUT1 deletion attenuates AAA development and rupture in mice. Rat aortic VSMC were obtained by the explant method. Media glucose consumption of cultured VSMCs was evaluated in the presence or absence of angiotensin II (AngII, 100 nM) stimulation and GLUT1 inhibitor BAY-876. GLUT1 floxed mice were crossed with tamoxifen-inducible SMMHC-Cre mice. At 6 weeks of age, mice were injected with 2 mg/kg tamoxifen for 5 days. Significant vascular GLUT1 silencing was confimed with immunofluorescent chemistry. As a control, tamoxifen-treated SMMHC-Cre male mice were utilized. At 8 weeks, AngII (1 μg/kg/min) was delivered for 4 weeks. In addition, mice were received 1 mg/mL BAPN during the first 2 weeks of AngII infusion. After 4weeks, all animals were euthanized and maximal external diameter of the abdominal aorta was measured. In cultured VSMC, glucose consumption increased by AngII was attenuated by pretreatment of 100 nM BAY-876. AngII plus BAPN significantly developed AAA in control mice. However, silencing of VSMC GLUT1 did not affect AAA development by AngII plus BAPN. The survival rate due to aortic rupture in VSMC GLUT1 silenced mice and control mice treated with BAPN and AngII were 60.0% and 57.1%, respectively. AngII induced hypertension in control mice and VSMC GLUT1 silenced mice. Although GLUT1 may be a primary VSMC GLUT to enhance glucose utilization in response to AngII stimulation, VSMC GLUT1 silencing did not alter AngII-dependent AAA development or rupture in a mouse model. Since pharmacological inhibition of GLUT
attenuated AAA and associated macrophage infiltration, it is possible that GLUT1 or other GLUT expressed in macrophages may contribute to development of AAA. In conclusion, VSMC GLUT1 silencing did not alter AngII-dependent AAA development or rupture in a mouse model.