A highly selective mPGES-1 inhibitor to block abdominal aortic aneurysm progression in the angiotensin mouse model
© 2024. The Author(s)..
Abdominal aortic aneurysm (AAA) is a deadly, permanent ballooning of the aortic artery. Pharmacological and genetic studies have pointed to multiple proteins, including microsomal prostaglandin E2 synthase-1 (mPGES-1), as potentially promising targets. However, it remains unknown whether administration of an mPGES-1 inhibitor can effectively attenuate AAA progression in animal models. There are still no FDA-approved pharmacological treatments for AAA. Current research stresses the importance of both anti-inflammatory drug targets and rigor of translatability. Notably, mPGES-1 is an inducible enzyme responsible for overproduction of prostaglandin E2 (PGE2)-a well-known principal pro-inflammatory prostanoid. Here we demonstrate for the first time that a highly selective mPGES-1 inhibitor (UK4b) can completely block further growth of AAA in the ApoE-/- angiotensin (Ang)II mouse model. Our findings show promise for the use of a mPGES-1 inhibitor like UK4b as interventional treatment of AAA and its potential translation into the clinical setting.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:14 |
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| Enthalten in: |
Scientific reports - 14(2024), 1 vom: 23. März, Seite 6959 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Weaver, Lauren M [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 25.03.2024 Date Revised 17.04.2024 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41598-024-57437-9 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM370113713 |
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| 520 | |a © 2024. The Author(s). | ||
| 520 | |a Abdominal aortic aneurysm (AAA) is a deadly, permanent ballooning of the aortic artery. Pharmacological and genetic studies have pointed to multiple proteins, including microsomal prostaglandin E2 synthase-1 (mPGES-1), as potentially promising targets. However, it remains unknown whether administration of an mPGES-1 inhibitor can effectively attenuate AAA progression in animal models. There are still no FDA-approved pharmacological treatments for AAA. Current research stresses the importance of both anti-inflammatory drug targets and rigor of translatability. Notably, mPGES-1 is an inducible enzyme responsible for overproduction of prostaglandin E2 (PGE2)-a well-known principal pro-inflammatory prostanoid. Here we demonstrate for the first time that a highly selective mPGES-1 inhibitor (UK4b) can completely block further growth of AAA in the ApoE-/- angiotensin (Ang)II mouse model. Our findings show promise for the use of a mPGES-1 inhibitor like UK4b as interventional treatment of AAA and its potential translation into the clinical setting | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Abdominal aortic aneurysm | |
| 650 | 4 | |a Aneurysm | |
| 650 | 4 | |a Anti-inflammation | |
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| 700 | 1 | |a Loftin, Charles D |e verfasserin |4 aut | |
| 700 | 1 | |a Zheng, Fang |e verfasserin |4 aut | |
| 700 | 1 | |a Zhan, Chang-Guo |e verfasserin |4 aut | |
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