OCR Text |
Show 124 KaChon Lei school of medicine and health sciences Fatty acid oxidation represents the major source of ATP generation in normal hearts. However, Glucose, which is mainly imported via GLUT1 and GLUT4 transporters, assumes greater importance in many clini-cally relevant circumstances such as during pressure overload hypertrophy (POH). Lifelong overexpression of GLUT1 in mouse hearts attenuates the development of contractile dysfunction after aortic constriction. Moreover, it is possible that long-term overexpression of GLUT1 could result in metabolic and transcrip-tional reprogramming in the heart, leading to the cardioprotective effects observed. Thus, in the pres-ent study we investigated if short-term GLUT1 overexpression in the adult heart was sufficient to confer cardioprotection in the setting of POH induced by transverse aortic constriction (TAC). We had therefore developed a model with inducible cardiomyocyte-restricted overexpression of GLUT1. GLUT1 overexpres-sion was induced 2 days prior to TAC or sham operation in 8-10 weeks-old control and transgenic mice. Eight weeks after the surgery, cardiac function was evaluated by echocardiography and left ventricle catheterization. Result suggested that short-term overexpression of GLUT1 attenuates the hypertrophic response, as shown by decreased heart weight and heart weight to body weight ratios and decreased mRNA expression of hypertrophy markers, such as ANP and BNP, when compared to control banded mice. Fibrosis also decreased in transgenic banded relative to control banded mice. However, contractile func-tion was not impaired by TAC in either group. Our data suggests that the protocol used in this experiment induced compensated hypertrophy, but not heart failure. Although short-term GLUT1 overexpression seemed to be protective, future experiments using a more severe TAC protocol is needed to verify if GLUT1 overexpression can protect the heart from developing contractile dysfunction induced by POH. INCREASED GLUT1 IN MURINE HEART PRESERVES MITOCHONDRIAL FUNCTION BUT IS INSUFFICIENT TO ATTENUATE PRESSURE OVERLOAD HYPERTROPHY KaChon Lei (Renata Alambert, Dale Abel) Department of Molecular Medicine, Human Genetics University of Utah UNDERGRADUATE RESEARCH ABSTRACTS Renata Alambert Dale Abel |