Cardioprotective Response and Senescence in Aged sEH Null Female Mice Exposed to LPS
Deterioration of physiological systems, like the cardiovascular system, occurs progressively with age impacting an individual's health and increasing susceptibility to injury and disease. Cellular senescence has an underlying role in age-related alterations and can be triggered by natural aging or prematurely by stressors such as the bacterial toxin, lipopolysaccharide (LPS). The metabolism of polyunsaturated fatty acids (PUFAs) by CYP450 enzymes produces numerous bioactive lipid mediators that can be further metabolized by soluble epoxide hydrolase (sEH) into diol metabolites, often with reduced biological effects. In our study, we observed age-related cardiac differences in female mice, where young mice demonstrated resistance to LPS injury, and genetic deletion or pharmacological inhibition of sEH using trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (tAUCB) attenuated LPS-induced cardiac dysfunction in aged female mice. Bulk RNA-sequencing analyses revealed transcriptomics differences in aged female hearts. Confirmatory analysis demonstrated changes to inflammatory and senescence genes markers such as Il-6, Mcp1, Il-1β, Nlrp3, p21, p16, SA-β-gal, and Gdf15 were attenuated in the hearts of aged female mice where sEH was deleted or inhibited. Collectively, these findings highlight the role of sEH in modulating the aging process of the heart, whereby targeting sEH is cardioprotective.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
American journal of physiology. Heart and circulatory physiology - (2024) vom: 05. Apr. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Yousef, Ala [VerfasserIn] |
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| Links: |
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| Themen: |
Aging |
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| Anmerkungen: |
Date Revised 05.04.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1152/ajpheart.00706.2023 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM370676556 |
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| 520 | |a Deterioration of physiological systems, like the cardiovascular system, occurs progressively with age impacting an individual's health and increasing susceptibility to injury and disease. Cellular senescence has an underlying role in age-related alterations and can be triggered by natural aging or prematurely by stressors such as the bacterial toxin, lipopolysaccharide (LPS). The metabolism of polyunsaturated fatty acids (PUFAs) by CYP450 enzymes produces numerous bioactive lipid mediators that can be further metabolized by soluble epoxide hydrolase (sEH) into diol metabolites, often with reduced biological effects. In our study, we observed age-related cardiac differences in female mice, where young mice demonstrated resistance to LPS injury, and genetic deletion or pharmacological inhibition of sEH using trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (tAUCB) attenuated LPS-induced cardiac dysfunction in aged female mice. Bulk RNA-sequencing analyses revealed transcriptomics differences in aged female hearts. Confirmatory analysis demonstrated changes to inflammatory and senescence genes markers such as Il-6, Mcp1, Il-1β, Nlrp3, p21, p16, SA-β-gal, and Gdf15 were attenuated in the hearts of aged female mice where sEH was deleted or inhibited. Collectively, these findings highlight the role of sEH in modulating the aging process of the heart, whereby targeting sEH is cardioprotective | ||
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| 700 | 1 | |a Korodimas, Jacob |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Andy |e verfasserin |4 aut | |
| 700 | 1 | |a Magor, Katharine E |e verfasserin |4 aut | |
| 700 | 1 | |a Seubert, John M |e verfasserin |4 aut | |
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