Development of pharmacotherapies for abdominal aortic aneurysms

Research output: Contribution to journalReview articlepeer-review

Abstract

The cardiovascular field is still searching for a treatment for abdominal aortic aneurysms (AAA). This inflammatory disease often goes undiagnosed until a late stage and associated rupture has a high mortality rate. No pharmacological treatment options are available. Three hallmark factors of AAA pathology include inflammation, extracellular matrix remodeling, and vascular smooth muscle dysfunction. Here we discuss drugs for AAA treatment that have been studied in clinical trials by examining the drug targets and data present for each drug's ability to regulate the aforementioned three hallmark pathways in AAA progression. Historically, drugs that were examined in interventional clinical trials for treatment of AAA were repurposed therapeutics. Novel treatments (biologics, small-molecule compounds etc.) have not been able to reach the clinic, stalling out in pre-clinical studies. Here we discuss the backgrounds of previous investigational drugs in hopes of better informing future development of potential therapeutics. Overall, the highlighted themes discussed here stress the importance of both centralized anti-inflammatory drug targets and rigor of translatability. Exceedingly few murine studies have examined an intervention-based drug treatment in halting further growth of an established AAA despite interventional treatment being the therapeutic approach taken to treat AAA in a clinical setting. Additionally, data suggest that a potentially successful drug target may be a central inflammatory biomarker. Specifically, one that can effectively modulate all three hallmark factors of AAA formation, not just inflammation. It is suggested that inhibiting PGE2 formation with an mPGES-1 inhibitor is a leading drug target for AAA treatment to this end.

Original languageEnglish
Article number113340
JournalBiomedicine and Pharmacotherapy
Volume153
DOIs
StatePublished - Sep 2022

Bibliographical note

Funding Information:
This work was supported in part by the funding of the Molecular Modeling and Biopharmaceutical Center at the University of Kentucky College of Pharmacy ; the National Science Foundation [Grant CHE-1111761 ]; and the National Institutes of Health [Grant P20 GM130456 ].

Publisher Copyright:
© 2022 The Authors

Keywords

  • Abdominal aortic aneurysms
  • Inflammation
  • Pharmacotherapy

ASJC Scopus subject areas

  • Pharmacology

Fingerprint

Dive into the research topics of 'Development of pharmacotherapies for abdominal aortic aneurysms'. Together they form a unique fingerprint.

Cite this