Abstract 2020: Vascular Glucose Transporter 1 Is Dispensable For Abdominal Aortic Aneurysm Induced By Angiotensin II

Abstract

Background: 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 cells (VSMC) leads to enhancement of atherosclerosis. However, the role of VSMC GLUT1 in AAA remains unclear. Hypothesis: VSMC GLUT1 deletion attenuates AAA development and rupture in mice. Goals/Aims: Our goal was to establish contribution of VSMC GLUT1 in AAA. Methods: The glucose consumption of cultured VSMCs was evaluated in the presence or absence of AngII 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 tamoxifen. As a control, tamoxifen-treated SMMHC-Cre male mice were utilized. At 8 weeks, angiotensin II (AngII, 1 μg/kg/min) was delivered for 4 weeks. In addition, mice 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. Results: In cultured VSMC, the glucose consumption increased by AngII was attenuated by pretreatment with GLUT1 inhibitor (media glucose 257.9±4.5 vs 238.9±6.2 mg/dL, p<0.05). AngII plus BAPN significantly developed AAA in control mice (diameter 1.05±0.07 vs 2.37±0.31mm, p<0.05). However, silencing of VSMC GLUT1 did not affect AAA development by AngII plus BAPN (2.41±0.46mm, p=0.66). 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 (p=0.820). AngII induced hypertension in control mice (102±3.8 vs 133±7.1mmHg, p<0.05) and VSMC GLUT1 silenced mice (149±11.4mmHg, p=0.99). Discussion 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 expressed in macrophages may contribute to development of AAA. Conclusion: VSMC GLUT1 silencing did not alter AngII-dependent AAA development in a mouse model.