A highly selective mPGES-1 inhibitor to block abdominal aortic aneurysm progression in the angiotensin mouse model

Lauren M. Weaver, Madeline J. Stewart, Kai Ding, Charles D. Loftin, Fang Zheng, Chang Guo Zhan

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number6959
JournalScientific Reports
Volume14
Issue number1
DOIs
StatePublished - Dec 2024

Bibliographical note

Publisher Copyright:
© The Author(s) 2024.

Keywords

  • Abdominal aortic aneurysm
  • Aneurysm
  • Anti-inflammation
  • mPGES-1 inhibitor
  • Prostaglandin E2

ASJC Scopus subject areas

  • General

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