PMID- 28104457
OWN - NLM
STAT- MEDLINE
DCOM- 20180604
LR  - 20181026
IS  - 1098-8823 (Print)
IS  - 1098-8823 (Linking)
VI  - 132
DP  - 2017 Sep
TI  - Genetic deletion of soluble epoxide hydrolase provides cardioprotective responses 
      following myocardial infarction in aged mice.
PG  - 47-58
LID - S1098-8823(17)30001-1 [pii]
LID - 10.1016/j.prostaglandins.2017.01.001 [doi]
AB  - BACKGROUND: 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. METHODS: 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. RESULTS: 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. 
      CONCLUSION: 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.
CI  - Copyright (c) 2017 Elsevier Inc. All rights reserved.
FAU - Jamieson, K Lockhart
AU  - Jamieson KL
AD  - Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Canada.
FAU - Samokhvalov, Victor
AU  - Samokhvalov V
AD  - Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Canada.
FAU - Akhnokh, Maria K
AU  - Akhnokh MK
AD  - Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Canada.
FAU - Lee, Kyra
AU  - Lee K
AD  - Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Canada.
FAU - Cho, Woo Jung
AU  - Cho WJ
AD  - Imaging Core Facility, Faculty of Medicine and Dentistry, University of Alberta, 
      Canada.
FAU - Takawale, Abhijit
AU  - Takawale A
AD  - Mazankowski Alberta Heart Institute, Faculty of Medicine, University of Alberta, 
      Canada; Department of Physiology, Faculty of Medicine and Dentistry, University 
      of Alberta, Canada.
FAU - Wang, Xiuhua
AU  - Wang X
AD  - Mazankowski Alberta Heart Institute, Faculty of Medicine, University of Alberta, 
      Canada; Department of Physiology, Faculty of Medicine and Dentistry, University 
      of Alberta, Canada.
FAU - Kassiri, Zamaneh
AU  - Kassiri Z
AD  - Mazankowski Alberta Heart Institute, Faculty of Medicine, University of Alberta, 
      Canada; Department of Physiology, Faculty of Medicine and Dentistry, University 
      of Alberta, Canada.
FAU - Seubert, John M
AU  - Seubert JM
AD  - 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.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20170116
PL  - United States
TA  - Prostaglandins Other Lipid Mediat
JT  - Prostaglandins & other lipid mediators
JID - 9808648
RN  - EC 3.3.2.- (Epoxide Hydrolases)
SB  - IM
MH  - Aging/*genetics
MH  - Animals
MH  - Epoxide Hydrolases/chemistry/*deficiency/*genetics
MH  - *Gene Deletion
MH  - Heart/physiopathology
MH  - Mice
MH  - Mitochondria/enzymology/metabolism
MH  - Myocardial Infarction/*enzymology/*genetics/pathology/physiopathology
MH  - Myocardium/*metabolism
MH  - Solubility
OTO - NOTNLM
OT  - Ageing
OT  - Cardiac
OT  - Cardioprotection
OT  - Ischemic injury
OT  - Mitochondria
OT  - Soluble epoxide hydrolase
EDAT- 2017/01/21 06:00
MHDA- 2018/06/05 06:00
CRDT- 2017/01/21 06:00
PHST- 2016/07/18 00:00 [received]
PHST- 2016/11/24 00:00 [revised]
PHST- 2017/01/03 00:00 [accepted]
PHST- 2017/01/21 06:00 [pubmed]
PHST- 2018/06/05 06:00 [medline]
PHST- 2017/01/21 06:00 [entrez]
AID - S1098-8823(17)30001-1 [pii]
AID - 10.1016/j.prostaglandins.2017.01.001 [doi]
PST - ppublish
SO  - Prostaglandins Other Lipid Mediat. 2017 Sep;132:47-58. doi: 
      10.1016/j.prostaglandins.2017.01.001. Epub 2017 Jan 16.