Basic Cardiovascular Sciences 2025  /  Poster Session and Reception 2  /  Sexual dimorphism in the cardioprotective effects toward myocardial infarction following genetic deletion of soluble epoxide hydrolase in aged mice
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Sexual dimorphism in the cardioprotective effects toward myocardial infarction following genetic deletion of soluble epoxide hydrolase in aged mice

Abstract Body:
Background: Myocardial infarction (MI) is a major cause of morbidity and mortality in elderly individuals, yet our understanding of age-related causes is limited. CYP450 epoxygenases metabolize polyunsaturated fatty acids into cardioprotective epoxylipids, which are readily degraded by soluble epoxide hydrolase (sEH). We have reported that sEH deletion is protective against MI-induced cardiac dysfunction in young mice, but its protective role in aged mice remains unclear. This study investigates if the cardioprotective effect of sEH deletion is also present in aged mice following MI injury.

Methods: Male and female 15-month-old wild-type (WT) and sEH null mice were subjected to permanent LAD ligation to induce MI. Assessments of frailty index, a measure of health status, and cardiac function were performed prior to, and 7 days post-MI. Hearts were collected for histological, molecular and biochemical analyses.

Results: Female sEH null mice, but not males, demonstrated significantly better frailty indices compared to WT female mice, suggesting better recovery from MI. Echocardiographic analyses revealed sEH null female mice had better post-MI cardiac function compared to WT counterparts (EF%: 26.9% vs. 37.6%). MI-induced cardiac and pulmonary hypertrophy were also attenuated in female sEH null mice but not males. Histological assessment of hearts using H&E and Masson’s Trichrome revealed better cardiac tissue architecture with denser tissue connection and less interstitial edema in the infarct border zone in sEH-null compared to WT female mice. Additionally, PSR staining analysis demonstrated thicker and more cross-linked collagen formations in the peri-infarct area, reflecting a better transition toward structured, stable extracellular matrix (ECM) remodeling. These findings were further supported by attenuated expression of ECM-related genes (Mmp2, Mmp14, Col1a1) in sEH null female hearts.

Conclusion: Our data highlight sex-specific differences in markers of cardiac injury following MI in aged mice. Notably, preliminary findings indicate that sEH inhibition confers greater cardioprotection in female but not in males mice, providing potential insights into the mechanism of age-related cardiac repair.
  • Fang, Liye  ( University of Alberta , Edmonton , Alberta , Canada )
  • Dong, Linyue  ( University of Alberta , Edmonton , Alberta , Canada )
  • Ussher, John  ( University of Alberta , Edmonton , Alberta , Canada )
  • Oudit, Gavin  ( Division of Cardiology, Mazankowski Alberta Heart Institute, University of Alberta , Edmonton , Alberta , Canada )
  • Kassiri, Zamaneh  ( University of Alberta , Edmonton , Alberta , Canada )
  • Seubert, John  ( University of Alberta , Edmonton , Alberta , Canada )
  • Yousef, Ala  ( University of Alberta , Edmonton , Alberta , Canada )
  • Wang, Faqi  ( University of Alberta , Edmonton , Alberta , Canada )
  • Huang, Andy  ( University of Alberta , Edmonton , Alberta , Canada )
  • Lee, Andy  ( University of Alberta , Edmonton , Alberta , Canada )
  • Tang, Xilan  ( University of Alberta , Edmonton , Alberta , Canada )
  • Li, Yingxi  ( University of Alberta , Edmonton , Alberta , Canada )
  • Atanasova, Nikki  ( University of Alberta , Edmonton , Alberta , Canada )
  • Kondraciuk, Patrick  ( University of Alberta , Edmonton , Alberta , Canada )
    • Author Disclosures:
    Liye Fang: DO NOT have relevant financial relationships | Linyue Dong: No Answer | John Ussher: No Answer | Gavin Oudit: No Answer | Zamaneh Kassiri: DO NOT have relevant financial relationships | John Seubert: DO NOT have relevant financial relationships | Ala Yousef: DO NOT have relevant financial relationships | Faqi Wang: No Answer | Andy Huang: DO NOT have relevant financial relationships | Andy Lee: DO NOT have relevant financial relationships | XILAN TANG: DO NOT have relevant financial relationships | Yingxi Li: No Answer | Nikki Atanasova: No Answer | Patrick Kondraciuk: No Answer
Meeting Info:

Basic Cardiovascular Sciences 2025

2025

Baltimore, Maryland

Session Info:

Poster Session and Reception 2

Thursday, 07/24/2025 , 04:30PM - 07:00PM

Poster Session and Reception

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