Metabolic Modulation in Heart Disease

• Author / Creator

  Sidhu, Vaninder K.

• Ischemic heart disease and pulmonary arterial hypertension are often accompanied by a drastic change in myocardial energy metabolism that favors fatty acid oxidation and glycolysis, respectively, over glucose oxidation. This form of energy production is both inefficient and detrimental to the myocardium. However, both the glucose and fatty acid oxidative pathways can be targeted to improve cardiac function. Specifically, decreasing fatty acid oxidation and/or increasing glucose metabolism can improve cardiac efficiency in these disease states. This thesis examines the metabolic changes in pulmonary hypertension and demonstrates the therapeutic advantages of metabolic modulation with dichloroacetate through restoring oxidative metabolism. We also investigate the effect of altered fatty acid metabolism on cardiac recovery following an ischemic episode using the acetyl CoA carboxylase-2 knockout mouse. Increased rates of fatty acid oxidation impair cardiac efficiency, but following ischemia these hearts sustain little injury owing to an adaptation in the 5’-AMPK–ACC–malonyl CoA pathway.

• Subjects / Keywords

  • Ischemic heart disease
  • Glucose oxidation
  • Myocardial energy metabolism
  • Pulmonary arterial hypertension
  • Fatty acid oxidation

• Graduation date

  Spring 2013

• Type of Item

  Thesis

• Degree

  Master of Science

• DOI

  https://doi.org/10.7939/R3C03D

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.