Affordable Access

deepdyve-link
Publisher Website

Cardioprotective effects of CYP-derived epoxy metabolites of docosahexaenoic acid involve limiting NLRP3 inflammasome activation 1.

Authors
  • Darwesh, Ahmed M1
  • Jamieson, K Lockhart1
  • Wang, Chuying1, 2
  • Samokhvalov, Victor1
  • Seubert, John M1, 3
  • 1 a Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB T6G 2R3, Canada. , (Canada)
  • 2 b School of Pharmaceutical Sciences, Changchun University of Chinese Medicine, Changchun, China. , (China)
  • 3 c Department of Pharmacology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2R3, Canada. , (Canada)
Type
Published Article
Journal
Canadian Journal of Physiology and Pharmacology
Publisher
Canadian Science Publishing
Publication Date
Jun 01, 2019
Volume
97
Issue
6
Pages
544–556
Identifiers
DOI: 10.1139/cjpp-2018-0480
PMID: 30326194
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Impaired mitochondrial function and activation of NLRP3 inflammasome cascade has a significant role in the pathogenesis of myocardial ischemia-reperfusion (IR) injury. The current study investigated whether eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), or their corresponding CYP epoxygenase metabolites 17,18-epoxyeicosatetraenoic acid (17,18-EEQ) and 19,20-epoxydocosapentaenoic acid (19,20-EDP) protect against IR injury. Isolated mouse hearts were perfused in the Langendorff mode with vehicle, DHA, 19,20-EDP, EPA, or 17,18-EEQ and subjected to 30 min of ischemia and followed by 40 min of reperfusion. In contrast with EPA and 17,18-EEQ, DHA and 19,20-EDP exerted cardioprotection, as shown by a significant improvement in postischemic functional recovery associated with significant attenuation of NLRP3 inflammasome complex activation and preserved mitochondrial function. Hearts perfused with DHA or 19,20-EDP displayed a marked reduction in localization of mitochondrial Drp-1 and Mfn-2 as well as maintained Opa-1 levels. DHA and 19,20-EDP preserved the activities of both the cytosolic Trx-1 and mitochondrial Trx-2. DHA cardioprotective effect was attenuated by the CYP epoxygenase inhibitor N-(methysulfonyl)-2-(2-propynyloxy)-benzenehexanamide. In conclusion, our data indicate a differential cardioprotective response between DHA, EPA, and their active metabolites toward IR injury. Interestingly, 19,20-EDP provided the best protection against IR injury via maintaining mitochondrial function and thereby reducing the detrimental NLRP3 inflammasome responses.

Report this publication

Statistics

Seen <100 times