changes in cardiac substrate transporters and metabolic proteins mirror the metabolic shift in patients with aortic stenosis心脏衬底转运蛋白和蛋白质代谢的变化反映主动脉瓣狭窄患者的代谢变化.pdfVIP

Changes in Cardiac Substrate Transporters and Metabolic Proteins Mirror the Metabolic Shift in Patients with Aortic Stenosis 1 2 1 1 3 Lisa C. Heather *, Neil J. Howell , Yaso Emmanuel , Mark A. Cole , Michael P. Frenneaux , Domenico Pagano2, Kieran Clarke1 1 Cardiac Metabolism Research Group, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom, 2 Department of Cardiothoracic Surgery, University Hospital NHS Foundation Trust, Birmingham, United Kingdom, 3 Institute of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom Abstract In the hypertrophied human heart, fatty acid metabolism is decreased and glucose utilisation is increased. We hypothesized that the sarcolemmal and mitochondrial proteins involved in these key metabolic pathways would mirror these changes, providing a mechanism to account for the modified metabolic flux measured in the human heart. Echocardiography was performed to assess in vivo hypertrophy and aortic valve impairment in patients with aortic stenosis (n = 18). Cardiac biopsies were obtained during valve replacement surgery, and used for western blotting to measure metabolic protein levels. Protein levels of the predominant fatty acid transporter, fatty acid translocase (FAT/CD36) correlated negatively with levels of the glucose transporters, GLUT1 and GLUT4. The decrease in FAT/CD36 was accompanied by decreases in the fatty acid binding proteins, FABPpm and H-FABP, the b-oxidation protein medium chain acyl-coenzyme A dehydrogenase, the Krebs cycle protein a-ketoglutarate dehydrogenase and the oxidative phosphorylation protein ATP synthase. FAT/CD36 and complex I of the electron transport chain were downregulated, whereas the glucose transporter GL