Epoxylipids and soluble epoxide hydrolase in heart diseases

Imig, John D.; Červenka, Luděk; Neckář, Jan

doi:10.1016/j.bcp.2021.114866

Cited by 16 publications

(16 citation statements)

References 101 publications

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“…We cannot not rule out that EPHX2 regulation of other EpFAs does not contribute, at least in part, to the development of cardiovascular disease or the postischemic recovery of heart function in vivo . The combination of omega-3 supplementation and EPHX2 inhibition may synergistically improve I/R recovery, as it does for other cardiovascular outcomes ( 47 ).…”

Section: Discussionmentioning

confidence: 99%

Disruption of Ephx2 in cardiomyocytes but not endothelial cells improves functional recovery after ischemia-reperfusion in isolated mouse hearts

Edin¹,

Gruzdev²,

Bradbury³

et al. 2023

Journal of Biological Chemistry

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Section: Discussionmentioning

confidence: 99%

Disruption of Ephx2 in cardiomyocytes but not endothelial cells improves functional recovery after ischemia-reperfusion in isolated mouse hearts

Edin¹,

Gruzdev²,

Bradbury³

et al. 2023

Journal of Biological Chemistry

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“…It has been demonstrated that TGF-β1 induces the expression of SPHK1 to stimulate collagen production in both cardiac fibroblasts and myofibroblasts through S1P signaling [ 54 , 55 ]. The Ephx2 gene encodes for soluble epoxide hydrolase (sEH) involved in the metabolism of arachidonic acid, a polyunsaturated fatty acid released into the cytosol in response to cardiac stressors [ 56 ]. sEH genetic ablation and pharmacological inhibition have been shown to exert cardioprotective actions in myocardial infarction and HF, improving mitochondrial function, reducing oxidative stress and inflammation, and opposing apoptosis [ 56 ].…”

Section: Discussionmentioning

confidence: 99%

“…The Ephx2 gene encodes for soluble epoxide hydrolase (sEH) involved in the metabolism of arachidonic acid, a polyunsaturated fatty acid released into the cytosol in response to cardiac stressors [ 56 ]. sEH genetic ablation and pharmacological inhibition have been shown to exert cardioprotective actions in myocardial infarction and HF, improving mitochondrial function, reducing oxidative stress and inflammation, and opposing apoptosis [ 56 ]. Although RAGE activation has been associated with lipid accumulation and peroxidation in several organs [ 57 , 58 , 59 ], its specific role in intramyocardial lipid accumulation remains unknown.…”

Section: Discussionmentioning

confidence: 99%

Effects of RAGE Deletion on the Cardiac Transcriptome during Aging

Scavello

Piacentini

Castiglione

et al. 2022

IJMS

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Cardiac aging is characterized by increased cardiomyocyte hypertrophy, myocardial stiffness, and fibrosis, which enhance cardiovascular risk. The receptor for advanced glycation end-products (RAGE) is involved in several age-related diseases. RAGE knockout (Rage−/−) mice show an acceleration of cardiac dimension changes and interstitial fibrosis with aging. This study identifies the age-associated cardiac gene expression signature induced by RAGE deletion. We analyzed the left ventricle transcriptome of 2.5-(Young), 12-(Middle age, MA), and 21-(Old) months-old female Rage−/− and C57BL/6N (WT) mice. By comparing Young, MA, and Old Rage−/− versus age-matched WT mice, we identified 122, 192, and 12 differently expressed genes, respectively. Functional inference analysis showed that RAGE deletion is associated with: (i) down-regulation of genes involved in antigen processing and presentation of exogenous antigen, adaptive immune response, and cellular responses to interferon beta and gamma in Young animals; (ii) up-regulation of genes related to fatty acid oxidation, cardiac structure remodeling and cellular response to hypoxia in MA mice; (iii) up-regulation of few genes belonging to complement activation and triglyceride biosynthetic process in Old animals. Our findings show that the age-dependent cardiac phenotype of Rage−/− mice is associated with alterations of genes related to adaptive immunity and cardiac stress pathways.

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“…Indeed, isolated and cultured vibrissae also grew longer when either the sEH was not expressed or the enzyme was inhibited. Since sEH metabolizes PUFA epoxides to their vicinal diols [ 47 ], LC–MS/MS was used to determine which PUFA metabolites in whisker follicles were affected by sEH deletion. Clear changes in only one epoxide/diol pair, i.e., 12,13-EpOME/DiHOME were detected, and of these, only the sEH substrate; 12,13-EpOME, stimulated whisker growth.…”

Section: Discussionmentioning

confidence: 99%

Role of the soluble epoxide hydrolase in the hair follicle stem cell homeostasis and hair growth

Naeem

Zukunft

Günther

et al. 2022

Pflugers Arch - Eur J Physiol

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Polyunsaturated fatty acids (PUFAs) are used as traditional remedies to treat hair loss, but the mechanisms underlying their beneficial effects are not well understood. Here, we explored the role of PUFA metabolites generated by the cytochrome P450/soluble epoxide hydrolase (sEH) pathway in the regulation of the hair follicle cycle. Histological analysis of the skin from wild-type and sEH−/− mice revealed that sEH deletion delayed telogen to anagen transition, and the associated activation of hair follicle stem cells. Interestingly, EdU labeling during the late anagen stage revealed that hair matrix cells from sEH−/− mice proliferated at a greater rate which translated into increased hair growth. Similar effects were observed in in vitro studies using hair follicle explants, where a sEH inhibitor was also able to augment whisker growth in follicles from wild-type mice. sEH activity in the dorsal skin was not constant but altered with the cell cycle, having the most prominent effects on levels of the linoleic acid derivatives 12,13-epoxyoctadecenoic acid (12,13-EpOME), and 12,13-dihydroxyoctadecenoic acid (12,13-DiHOME). Fitting with this, the sEH substrate 12,13-EpOME significantly increased hair shaft growth in isolated anagen stage hair follicles, while its diol; 12,13-DiHOME, had no effect. RNA sequencing of isolated hair matrix cells implicated altered Wnt signaling in the changes associated with sEH deletion. Taken together, our data indicate that the activity of the sEH in hair follicle changes during the hair follicle cycle and impacts on two stem cell populations, i.e., hair follicle stem cells and matrix cells to affect telogen to anagen transition and hair growth.

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Epoxylipids and soluble epoxide hydrolase in heart diseases

Cited by 16 publications

References 101 publications

Disruption of Ephx2 in cardiomyocytes but not endothelial cells improves functional recovery after ischemia-reperfusion in isolated mouse hearts

Disruption of Ephx2 in cardiomyocytes but not endothelial cells improves functional recovery after ischemia-reperfusion in isolated mouse hearts

Effects of RAGE Deletion on the Cardiac Transcriptome during Aging

Role of the soluble epoxide hydrolase in the hair follicle stem cell homeostasis and hair growth

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