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Isolation of Mouse Interstitial Valve Cells to Study the Calcification of the Aortic Valve In Vitro
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Isolation of Mouse Interstitial Valve Cells to Study the Calcification of the Aortic Valve In Vitro

Published on: May 10, 2021

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Celecoxib Is Associated With Dystrophic Calcification and Aortic Valve Stenosis

Meghan A Bowler1, Michael A Raddatz1, Camryn L Johnson1

  • 1Department of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee.

JACC. Basic to Translational Science
|May 8, 2019
PubMed

Insights

Celecoxib, investigated for calcific aortic valve disease, unexpectedly worsened it in vitro. A retrospective analysis found celecoxib use uniquely associated with aortic stenosis.

Area of Science:

  • Cardiovascular Biology
  • Pharmacology
  • Biomaterials Science

Background:

  • Calcific aortic valve disease (CAVD) is a degenerative condition requiring valve replacement.
  • Cadherin-11 is a potential therapeutic target for CAVD.
  • Celecoxib, a cyclooxygenase-2 inhibitor, targets Cadherin-11.

Purpose of the Study:

  • To investigate celecoxib as a potential therapeutic for CAVD.
  • To evaluate the in vitro and in vivo effects of celecoxib on CAVD.
  • To determine the association between celecoxib use and aortic stenosis.

Main Methods:

  • In vitro cell culture models to assess myofibroblast activation and calcific nodule formation.
  • Retrospective analysis of electronic medical records comparing celecoxib, ibuprofen, and naproxen.
  • Statistical analysis to identify unique associations between drug use and aortic stenosis.

Main Results:

  • Celecoxib treatment in vitro induced myofibroblast activation and calcific nodule formation.
  • Retrospective analysis revealed a unique association between celecoxib use and aortic stenosis.
  • No such association was found for ibuprofen or naproxen.

Conclusions:

  • Celecoxib may exacerbate calcific aortic valve disease.
  • Further investigation is needed to understand the mechanism of celecoxib's adverse effects.
  • Current therapeutic strategies targeting Cadherin-11 with celecoxib require re-evaluation.
Keywords:
ANOVA, analysis of varianceAS, aortic stenosisAVEC, aortic valve endothelial cellAVIC, aortic valve interstitial cellCAVD, calcific aortic valve diseaseCDH11, cadherin-11CN, calcific noduleCOX2, cyclooxygenase-2EMR, electronic medical recordFDA, Food and Drug AdministrationOR, odds ratioSMA, smooth muscle actinTGF, transforming growth factorVUMC, Vanderbilt University Medical Centeraortic stenosisaortic valvecalcificationcelecoxib

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