| OCR Text |
Show THE UNIVERSITY OF UTAH HONORS COLLEGE INCREASED GLUT1 EXPRESSION IN MOUSE CARDIOMYOCYTES PRESERVES MITOCHONDRIAL FUNCTION BUT IS INSUFFICIENTTO ATTENUATE PRESSURE OVERLOAD-INDUCED CONTRACTILE DYSFUNCTION KaChon Lei ( Renata Alambert, Dale Abel) Division of Endocrinology, Diabetes and Metabolism University of Utah Lifelong over-expression of GLUT1 transporter in the heart has been shown to preserve contractile function after aortic constriction. However it is unclear whether this protective effect is due to GLUT1 overexpression itself or due to reprogramming of heart metabolism as a result of long-term increased glucose utilization. We, therefore generated mice with cardiomyocyte-restricted inducible overexpression of GLUT1 (G1 HA) to test if short-term GLUT1 overexpression at the onset of pressure overload hypertrophy (POH) is sufficient to prevent the progression to heart failure in a model of POH. Six-week old mice were subjected to transverse aortic constriction (TAC) to induce POH. GLUT1 transgene expression was initiated 2 days prior to TAC surgery and resulted in a 4-fold increase in cardiac GLUT1 protein levels relative to controls. Four weeks after TAC, cardiac contractile function was equivalently impaired in control and G 1 H A mice, as shown by increased left ventricular developed pressure and decreased in maximal dp/dt ratio. In contrast, mitochondrial function following TAC was preserved and fibrosis was significantly decreased in G 1 H A mice relative to control. In summary, our data suggest that a short-term increase in GLUT1-mediated glucose uptake preserves mitochondrial function and attenuates pathological remodeling, but does not prevent cardiac dysfunction following POH. |
