Upregulation of cardiac mitoch0ondrial function in atherosclerotic mice

Atherosclerosis is considered as vascular disease and metabolic adaptation in the heart that occurs before coronary arteries become occluded are poorly characterized. The aim of this study was to analyze metabolic adaptations in the hearts of atherosclerotic mice. Atherosclerotic mice (ApoE/LDLR--/--) and wild type controls (WT) were analyzed for cardiac protein pattern using non-targeted mass spectrometric proteomics, for glucose and leucine  in vivo contribution to cardiac Krebs cycle with stable isotopomer/liquid chromatography/mass spectrometry, for cardiac high energy phosphates by HPLC and for ECG response to hypoxia. Cardiac proteome analysis revealed increased content of mitochondrial proteins, including enzymes responsible for fatty acid oxidation and branched chain amino acids oxidation in ApoE/LDLR--/--. This correlated with increased entry of leucine and decreased entry of glucose and into cardiac Krebs cycle estimated in vivo. No differences were noted in cardiac in ATP/ADP or Phosphocreatine/creatine ratios under normoxic conditions. However, hypoxia induced profound ST segment ECG changes in ApoE/LDLR--/-- in contrast to WT. This study highlights increased mitochondrial activity in hearts of atherosclerotic mice demonstrated by protein content and metabolic function analysis. While energy equilibrium was balanced under normoxic conditions, atherosclerotic hearts were more sensitive to hypoxia.