Author + information
- Received November 13, 2018
- Revision received December 11, 2018
- Accepted December 12, 2018
- Published online April 29, 2019.
- Meghan A. Bowler, PhDa,∗,
- Michael A. Raddatz, BSa,∗,
- Camryn L. Johnson, BSa,
- Brian R. Lindman, MD, MScb and
- W. David Merryman, PhDa,∗ ()
- aDepartment of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee
- bStructural Heart and Valve Center, Vanderbilt University Medical Center, Nashville, Tennessee
- ↵∗Address for correspondence:
Dr. W. David Merryman, Vanderbilt University, 2213 Garland Avenue, 9445D MRB4, Nashville, Tennessee 37232.
• Celecoxib use is associated with diagnosis of aortic stenosis in analysis of electronic medical records.
• Celecoxib treatment increases dystrophic calcification of aortic valve interstitial cells in vitro.
• Dimethyl celecoxib, which binds CDH11, prevents TGF-β1–mediated calcification of aortic valve interstitial cells in vitro.
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.
↵∗ Dr. Bowler and Mr. Raddatz contributed equally to this work, and are joint first authors.
This content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health (NIH), the National Science Foundation (NSF), or Vanderbilt University. This work was funded by NIH grants HL135790, HL115103, and GM007347, American Heart Association grant 18PRE34070125, and NSF grants 1055384 and 2013170175. The datasets used for the analyses described were obtained from Vanderbilt University Medical Center’s BioVU, which is supported by numerous sources: institutional funding, private agencies, and federal grants. These include the NIH-funded Shared Instrumentation grant S10RR025141, and CTSA grants UL1TR002243, UL1TR000445, and UL1RR024975. The clinical datasets used for the analyses described were obtained from Vanderbilt University Medical Center’s Synthetic Derivative. Dr. Lindman has received research grants from Edwards Lifesciences and Roche Diagnostics; served on scientific advisory boards for Roche Diagnostics; and has been a consultant to Medtronic and Roche Diagnostics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
All authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Basic to Translational Science author instructions page.
- Received November 13, 2018.
- Revision received December 11, 2018.
- Accepted December 12, 2018.
- 2019 The Authors