Sex differences in specialized pro-resolving lipid mediators and their receptors in abdominal aortic aneurysms
Objective: In this study, we tested the hypothesis that endogenous expression of specialized pro-resolving lipid mediators (SPMs) that facilitate the resolution of inflammation, specifically Resolvin D1and -D2, as well as Maresin1 (MaR1), can impact abdominal aortic aneurysm (AAA) formation and prog...
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| Format: | Članak |
| Jezik: | English |
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Elsevier
2023-01-01
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| Serija: | JVS - Vascular Science |
| Teme: | |
| Online pristup: | http://www.sciencedirect.com/science/article/pii/S2666350323000111 |
| _version_ | 1827395223399956480 |
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| author | Amanda C. Filiberto, MD Victoria Leroy, BS Zachary Ladd, BS Gang Su, MD Craig T. Elder, MD Eric Y. Pruitt, MD Guanyi Lu, MD Joseph Hartman, BS Ali Zarrinpar, MD, PhD Timothy J. Garrett, PhD Ashish K. Sharma, MBBS, PhD Gilbert R. Upchurch, Jr., MD |
| author_facet | Amanda C. Filiberto, MD Victoria Leroy, BS Zachary Ladd, BS Gang Su, MD Craig T. Elder, MD Eric Y. Pruitt, MD Guanyi Lu, MD Joseph Hartman, BS Ali Zarrinpar, MD, PhD Timothy J. Garrett, PhD Ashish K. Sharma, MBBS, PhD Gilbert R. Upchurch, Jr., MD |
| author_sort | Amanda C. Filiberto, MD |
| collection | DOAJ |
| description | Objective: In this study, we tested the hypothesis that endogenous expression of specialized pro-resolving lipid mediators (SPMs) that facilitate the resolution of inflammation, specifically Resolvin D1and -D2, as well as Maresin1 (MaR1), can impact abdominal aortic aneurysm (AAA) formation and progression in a sex-specific manner. Methods: SPM expression was quantified in aortic tissue from human AAA samples and from a murine in vivo AAA model via liquid chromatography-tandem mass spectrometry. mRNA expression for SPM receptors FPR2, LGR6, and GPR18 were quantified by real-time polymerase chain reaction. A Student t test with nonparametric Mann-Whitney or Wilcoxon test was used for pair-wise comparisons of groups. One-way analysis of variance after post hoc Tukey test was used to determine the differences among multiple comparative groups. Results: Human aortic tissue analysis revealed a significant decrease in RvD1 levels in male AAAs compared with controls, whereas FPR2 and LGR6 receptor expressions were downregulated in male AAAs compared with male controls. In vivo studies of elastase-treated mice showed higher levels of RvD2 and MaR1 as well as the SPM precursors, omega-3 fatty acids DHA and EPA, in aortic tissue from males compared with females. FPR2 expression was increased in elastase-treated females compared with males. Conclusions: Our findings demonstrate that specific differences in SPMs and their associated G-protein coupled receptors exist between sexes. These results indicate the relevance of SPM-mediated signaling pathways in sex differences impacting the pathogenesis of AAAs. : Clinical Relevance: AAAs are a substantial clinical problem and can lead to sudden aortic rupture and death. Recent studies have shown a critical role for sex disparity during AAA formation, as female sex has a lower incidence of aortic aneurysm disease, but their outcomes following intervention appear to be worse. Few studies have examined the potential causes that underlie these differences. In this study, we tested the hypothesis that sex differences in endogenous SPM expression and their receptors exist between males and females and that this difference could be associated with AAA formation. |
| first_indexed | 2024-03-08T18:29:48Z |
| format | Article |
| id | doaj.art-7e41a34814df48e38038f585b85fed68 |
| institution | Directory Open Access Journal |
| issn | 2666-3503 |
| language | English |
| last_indexed | 2024-03-08T18:29:48Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | JVS - Vascular Science |
| spelling | doaj.art-7e41a34814df48e38038f585b85fed682023-12-30T04:44:51ZengElsevierJVS - Vascular Science2666-35032023-01-014100107Sex differences in specialized pro-resolving lipid mediators and their receptors in abdominal aortic aneurysmsAmanda C. Filiberto, MD0Victoria Leroy, BS1Zachary Ladd, BS2Gang Su, MD3Craig T. Elder, MD4Eric Y. Pruitt, MD5Guanyi Lu, MD6Joseph Hartman, BS7Ali Zarrinpar, MD, PhD8Timothy J. Garrett, PhD9Ashish K. Sharma, MBBS, PhD10Gilbert R. Upchurch, Jr., MD11Department of Surgery, University of Florida, Gainesville, FLDepartment of Surgery, University of Florida, Gainesville, FLDepartment of Surgery, University of Florida, Gainesville, FLDepartment of Surgery, University of Florida, Gainesville, FLDepartment of Surgery, University of Florida, Gainesville, FLDepartment of Surgery, University of Florida, Gainesville, FLDepartment of Surgery, University of Florida, Gainesville, FLDepartment of Surgery, University of Florida, Gainesville, FLDepartment of Surgery, University of Florida, Gainesville, FLDepartment of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FLDepartment of Surgery, University of Florida, Gainesville, FL; Aortic Disease Center, University of Florida, Gainesville, FLDepartment of Surgery, University of Florida, Gainesville, FL; Aortic Disease Center, University of Florida, Gainesville, FL; Correspondence: Gilbert R. Upchurch Jr, MD, Department of Surgery, University of Florida, PO Box 100286, Gainesville, FL 32610-0128Objective: In this study, we tested the hypothesis that endogenous expression of specialized pro-resolving lipid mediators (SPMs) that facilitate the resolution of inflammation, specifically Resolvin D1and -D2, as well as Maresin1 (MaR1), can impact abdominal aortic aneurysm (AAA) formation and progression in a sex-specific manner. Methods: SPM expression was quantified in aortic tissue from human AAA samples and from a murine in vivo AAA model via liquid chromatography-tandem mass spectrometry. mRNA expression for SPM receptors FPR2, LGR6, and GPR18 were quantified by real-time polymerase chain reaction. A Student t test with nonparametric Mann-Whitney or Wilcoxon test was used for pair-wise comparisons of groups. One-way analysis of variance after post hoc Tukey test was used to determine the differences among multiple comparative groups. Results: Human aortic tissue analysis revealed a significant decrease in RvD1 levels in male AAAs compared with controls, whereas FPR2 and LGR6 receptor expressions were downregulated in male AAAs compared with male controls. In vivo studies of elastase-treated mice showed higher levels of RvD2 and MaR1 as well as the SPM precursors, omega-3 fatty acids DHA and EPA, in aortic tissue from males compared with females. FPR2 expression was increased in elastase-treated females compared with males. Conclusions: Our findings demonstrate that specific differences in SPMs and their associated G-protein coupled receptors exist between sexes. These results indicate the relevance of SPM-mediated signaling pathways in sex differences impacting the pathogenesis of AAAs. : Clinical Relevance: AAAs are a substantial clinical problem and can lead to sudden aortic rupture and death. Recent studies have shown a critical role for sex disparity during AAA formation, as female sex has a lower incidence of aortic aneurysm disease, but their outcomes following intervention appear to be worse. Few studies have examined the potential causes that underlie these differences. In this study, we tested the hypothesis that sex differences in endogenous SPM expression and their receptors exist between males and females and that this difference could be associated with AAA formation.http://www.sciencedirect.com/science/article/pii/S2666350323000111Abdominal aortic aneurysmAortic aneurysmsLipid mediatorsResolution of inflammationResolvinsSex differences |
| spellingShingle | Amanda C. Filiberto, MD Victoria Leroy, BS Zachary Ladd, BS Gang Su, MD Craig T. Elder, MD Eric Y. Pruitt, MD Guanyi Lu, MD Joseph Hartman, BS Ali Zarrinpar, MD, PhD Timothy J. Garrett, PhD Ashish K. Sharma, MBBS, PhD Gilbert R. Upchurch, Jr., MD Sex differences in specialized pro-resolving lipid mediators and their receptors in abdominal aortic aneurysms JVS - Vascular Science Abdominal aortic aneurysm Aortic aneurysms Lipid mediators Resolution of inflammation Resolvins Sex differences |
| title | Sex differences in specialized pro-resolving lipid mediators and their receptors in abdominal aortic aneurysms |
| title_full | Sex differences in specialized pro-resolving lipid mediators and their receptors in abdominal aortic aneurysms |
| title_fullStr | Sex differences in specialized pro-resolving lipid mediators and their receptors in abdominal aortic aneurysms |
| title_full_unstemmed | Sex differences in specialized pro-resolving lipid mediators and their receptors in abdominal aortic aneurysms |
| title_short | Sex differences in specialized pro-resolving lipid mediators and their receptors in abdominal aortic aneurysms |
| title_sort | sex differences in specialized pro resolving lipid mediators and their receptors in abdominal aortic aneurysms |
| topic | Abdominal aortic aneurysm Aortic aneurysms Lipid mediators Resolution of inflammation Resolvins Sex differences |
| url | http://www.sciencedirect.com/science/article/pii/S2666350323000111 |
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