title: Genetic deletion of soluble epoxide hydrolase provides cardioprotective responses following myocardial infarction in aged mice.
abstract: Pathophysiological responses, including cardiovascular complications, often alter with age. Cardioprotective effects of epoxyeicosatrienoic acids (EETs) toward acute myocardial ischemia-reperfusion injury have been well documented. However, biological relevance of EET-evoked cardioprotection in the ageing myocardium remains unknown. EETs are metabolized to less active metabolites by the enzyme soluble epoxide hydrolase (sEH). This study uses permanent occlusion of the left anterior descending artery (LAD) in young and aged sEH null and WT mice to compare cardiac and mitochondrial function following ischemic injury.
  
  
  
  Age-matched 16 month old (aged) and 3 month old (young) sEH null and littermate wild-type (WT) mice were subjected to permanent occlusion of the left anterior descending coronary artery. Echocardiography was used to assess cardiac structure and function prior-to and 7days post-myocardial infarction with tetrazolium chloride staining to determine infarct size. Mitochondrial ultrastructure was obtained using electron microscopy. Caspase-3, 20S proteasome, aconitase and mitochondrial ETC enzymatic activities were ascertained using established protocols. Mitochondrial respiration was assessed using a Clark electrode in permeabilized cardiac fibers to obtain respiratory control ratios.
  
  
  
  Markers of cell injury, mitochondrial efficiency and overall cardiac function were preserved in aged sEH null mice, although less robustly than in their young counterparts. While aged animals of both genotypes demonstrated a similar overall age-related decline, sEH deletion consistently demonstrated protection from myocardial ischemic injury regardless of age.
  
  
  
  Our data demonstrates the protection originating from sEH deletion in aged mice was markedly reduced compared to young animals, signifying unavoidable detrimental consequences of biological ageing on cardiac function.
authors.affiliation: Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Canada.
authors.forename: K Lockhart
authors.initials: KL
authors.lastname: Jamieson
authors.affiliation: Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Canada.
authors.forename: Victor
authors.initials: V
authors.lastname: Samokhvalov
authors.affiliation: Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Canada.
authors.forename: Maria K
authors.initials: MK
authors.lastname: Akhnokh
authors.affiliation: Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Canada.
authors.forename: Kyra
authors.initials: K
authors.lastname: Lee
authors.affiliation: Imaging Core Facility, Faculty of Medicine and Dentistry, University of Alberta, Canada.
authors.forename: Woo Jung
authors.initials: WJ
authors.lastname: Cho
authors.affiliation: Mazankowski Alberta Heart Institute, Faculty of Medicine, University of Alberta, Canada; Department of Physiology, Faculty of Medicine and Dentistry, University of Alberta, Canada.
authors.forename: Abhijit
authors.initials: A
authors.lastname: Takawale
authors.affiliation: Mazankowski Alberta Heart Institute, Faculty of Medicine, University of Alberta, Canada; Department of Physiology, Faculty of Medicine and Dentistry, University of Alberta, Canada.
authors.forename: Xiuhua
authors.initials: X
authors.lastname: Wang
authors.affiliation: Mazankowski Alberta Heart Institute, Faculty of Medicine, University of Alberta, Canada; Department of Physiology, Faculty of Medicine and Dentistry, University of Alberta, Canada.
authors.forename: Zamaneh
authors.initials: Z
authors.lastname: Kassiri
authors.affiliation: Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Canada; Mazankowski Alberta Heart Institute, Faculty of Medicine, University of Alberta, Canada; Department of Pharmacology, Faculty of Medicine and Dentistry, University of Alberta, Canada. Electronic address: jseubert@ualberta.ca.
authors.forename: John M
authors.initials: JM
authors.lastname: Seubert
mesh_terms: D000375:Aging / Q000235:genetics*; D000818:Animals; D004851:Epoxide Hydrolases / Q000737:chemistry / Q000172:deficiency* / Q000235:genetics*; D017353:Gene Deletion; D006321:Heart / Q000503:physiopathology; D051379:Mice; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism; D009203:Myocardial Infarction / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism*; D012995:Solubility
chemical_list: D004851:Epoxide Hydrolases
keywords: Ageing; Cardiac; Cardioprotection; Ischemic injury; Mitochondria; Soluble epoxide hydrolase