Calcific aortic valve disease is a progressive fibrocalcific process that can only be treated with valve replacement. Cadherin-11 has recently been identified as a potential therapeutic target for calcific aortic valve disease. The already approved drug celecoxib, a cyclooxygenase-2 inhibitor, binds cadherin-11, and was investigated as a therapeutic against calcific aortic valve disease. Unexpectedly, celecoxib treatment led to hallmarks of myofibroblast activation and calcific nodule formation in vitro. Retrospective electronic medical record analysis of celecoxib, ibuprofen, and naproxen revealed a unique association of celecoxib use and aortic stenosis.
Keywords: ANOVA, analysis of variance; AS, aortic stenosis; AVEC, aortic valve endothelial cell; AVIC, aortic valve interstitial cell; CAVD, calcific aortic valve disease; CDH11, cadherin-11; CN, calcific nodule; COX2, cyclooxygenase-2; EMR, electronic medical record; FDA, Food and Drug Administration; OR, odds ratio; SMA, smooth muscle actin; TGF, transforming growth factor; VUMC, Vanderbilt University Medical Center; aortic stenosis; aortic valve; calcification; celecoxib.