title: Absence of malonyl coenzyme A decarboxylase in mice increases cardiac glucose oxidation and protects the heart from ischemic injury.
abstract: BACKGROUND
  Acute pharmacological inhibition of cardiac malonyl coenzyme A decarboxylase (MCD) protects the heart from ischemic damage by inhibiting fatty acid oxidation and stimulating glucose oxidation. However, it is unknown whether chronic inhibition of MCD results in altered cardiac function, energy metabolism, or ischemic cardioprotection.
  
  
  RESULTS
  Mcd-deficient mice were produced and assessed for in vivo cardiac function as well as ex vivo cardiac function, energy metabolism, and ischemic tolerance. In vivo and ex vivo cardiac function was similar in wild-type and mcd-/- mice. Ex vivo working hearts from mcd-/- and wild-type mice displayed no significant differences in rates of fatty acid oxidation, glucose oxidation, or glycolysis. However, cardiac deletion of mcd resulted in an increased expression of genes regulating fatty acid utilization that may compensate for the loss of MCD protein and likely contributes to the absence of changes in energy metabolism in the aerobic heart. Despite the lack of changes in fatty acid utilization, hearts from mcd-/- mice displayed a marked preference for glucose utilization after ischemia, which correlated with a significant cardioprotection of ischemic hearts from mcd-/- mice compared with wild-type mice.
  
  
  CONCLUSIONS
  Deletion of MCD markedly increases glucose oxidation and improves functional recovery of the heart after ischemia. As a result, chronic pharmacological inhibition of MCD may be a viable approach to treat myocardial ischemia.
authors.affiliation: Cardiovascular Research Group, Department of Pediatrics, Faculty of Medicine, University of Alberta, Edmonton, Alberta, Canada, T6G 2S2. Jason.Dyck@UAlberta.ca
authors.forename: Jason R B
authors.initials: JR
authors.lastname: Dyck
authors.forename: Teresa A
authors.initials: TA
authors.lastname: Hopkins
authors.forename: Sebastien
authors.initials: S
authors.lastname: Bonnet
authors.forename: Evangelos D
authors.initials: ED
authors.lastname: Michelakis
authors.forename: Martin E
authors.initials: ME
authors.lastname: Young
authors.forename: Miho
authors.initials: M
authors.lastname: Watanabe
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Kawase
authors.forename: Kou-ichi
authors.initials: K
authors.lastname: Jishage
authors.forename: Gary D
authors.initials: GD
authors.lastname: Lopaschuk
mesh_terms: D000818:Animals; D002262:Carboxy-Lyases / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D005947:Glucose / Q000378:metabolism*; D006321:Heart / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017202:Myocardial Ischemia / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control*; D010084:Oxidation-Reduction
chemical_list: D002262:Carboxy-Lyases; C021532:malonyl-CoA decarboxylase; D005947:Glucose