ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2011
Endothelial expression of human cytochrome P450 epoxygenase CYP2C8 increases susceptibility to ischemia-reperfusion injury in isolated mouse heart.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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78 citing papers in PubMed, 119 citations in OpenAlex.
- Endothelial expression of human soluble epoxide hydrolase worsens acute microvascular and tissue injury after stroke in female mice with early-stage diabetes mellitus.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026Article
- Recipient plasma metabolomics as a predictor of heart transplant severe primary graft dysfunction.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2026Article
- Regulation of P450-derived epoxy fatty acids in cardiovascular diseases.Redox biochemistry and chemistry · 2025Article
- The Octadecanoids: Synthesis and Bioactivity of 18-Carbon Oxygenated Fatty Acids in Mammals, Bacteria, and Fungi.Chemical reviews · 2025Review
- Overexpression of soluble epoxide hydrolase reduces post-ischemic recovery of cardiac contractile function.Biochemical pharmacology · 2024Article
- Effects of sEH inhibition on the eicosanoid and cytokine storms in SARS-CoV-2-infected mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Oxylipins as therapeutic indicators of herbal medicines in cardiovascular diseases: a review.Frontiers in pharmacology · 2024Review
- Impact of Reperfusion on Plasma Oxylipins in ST-Segment Elevation Myocardial Infarction.Metabolites · 2023Article
- The Plasma Oxylipin Signature Provides a Deep Phenotyping of Metabolic Syndrome Complementary to the Clinical Criteria.International journal of molecular sciences · 2022Article
- Cytochrome P450 oxidase 2J inhibition suppresses choroidal neovascularization in mice.Metabolism: clinical and experimental · 2022Article
- Anthracycline derivatives inhibit cardiac CYP2J2.Journal of inorganic biochemistry · 2022Article
- Untargeted Metabolomics Analysis of the Serum Metabolic Signature of Childhood Obesity.Nutrients · 2022Article
- Endothelial deletion of the cytochrome P450 reductase leads to cardiac remodelling.Frontiers in physiology · 2022Article
- Changes in the Left Ventricular Eicosanoid Profile in Human Dilated Cardiomyopathy.Frontiers in cardiovascular medicine · 2022Article
- Cytochrome P450-derived linoleic acid metabolites EpOMEs and DiHOMEs: a review of recent studies.The Journal of nutritional biochemistry · 2020Review
- Mitochondrial Dysfunction and Inflammaging in Heart Failure: Novel Roles of CYP-Derived Epoxylipids.Cells · 2020Review
- Eicosanoids and Oxidative Stress in Diabetic Retinopathy.Antioxidants (Basel, Switzerland) · 2020Review
- Review
- Assessment of soluble epoxide hydrolase activity in vivo: A metabolomic approach.Prostaglandins & other lipid mediators · 2020Article
- Article
18 more citing papers are in PubMed but not listed here.
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12 authors at 4 institutions in 1 country.
Funding
Abstract
Cytochrome P450 (CYP) epoxygenases CYP2C8 and CYP2J2 generate epoxyeicosatrienoic acids (EETs) from arachidonic acid. Mice with expression of CYP2J2 in cardiomyocytes (αMHC-CYP2J2 Tr) or treated with synthetic EETs have increased functional recovery after ischemia/reperfusion (I/R); however, no studies have examined the role of cardiomyocyte- vs. endothelial-derived EETs or compared the effects of different CYP epoxygenase isoforms in the ischemic heart. We generated transgenic mice with increased endothelial EET biosynthesis (Tie2-CYP2C8 Tr and Tie2-CYP2J2 Tr) or EET hydrolysis (Tie2-sEH Tr). Compared to wild-type (WT), αMHC-CYP2J2 Tr hearts showed increased recovery of left ventricular developed pressure (LVDP) and decreased infarct size after I/R. In contrast, LVDP recovery and infarct size were unchanged in Tie2-CYP2J2 Tr and Tie2-sEH Tr hearts. Surprisingly, compared to WT, Tie2-CYP2C8 Tr hearts had significantly reduced LVDP recovery (from 21 to 14%) and increased infarct size after I/R (from 51 to 61%). Tie2-CYP2C8 Tr hearts also exhibited increased reactive oxygen species (ROS) generation, dihydroxyoctadecenoic acid (DiHOME) formation, and coronary resistance after I/R. ROS scavengers and CYP2C8 inhibition reversed the detrimental effects of CYP2C8 expression in Tie2-CYP2C8 Tr hearts. Treatment of WT hearts with 250 nM 9,10-DiHOME decreased LVDP recovery compared to vehicle (16 vs. 31%, respectively) and increased coronary resistance after I/R. These data demonstrate that increased ROS generation and enhanced DiHOME synthesis by endothelial CYP2C8 impair functional recovery and mask the beneficial effects of increased EET production following I/R.
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