The cycloxygenase 2 (COX-2) story: It's time to explain, not inflame

Guillermo Salinas, Umamahesh C. Rangasetty, Barry F. Uretsky, Yochai Birnbaum

Research output: Contribution to journalArticlepeer-review

43 Scopus citations


Despite initial promising reports that anti-inflammatory properties of cycloxygenase-2 (COX-2) inhibitors may confer anti-atherosclerosis effects and stabilize the atherosclerotic plaque, subsequent data from long-term clinical trials have shown that selective COX-2 inhibitors are associated with increased risk of cardiovascular events. The commonly cited explanation is that selective inhibition of COX-2 leads to depletion of prostacyclin, whereas the production of pro-thrombotic thromboxane by means of cycloxygenase-1 (COX-1) is unopposed. This hypothesis seems unlikely as the overall explanation, because low-dose aspirin does not decrease the increased risk associated with COX-2 inhibitors. Moreover, the risk associated with nonselective COX inhibitors may be similar to selective COX-2 inhibitors. Alternative hypotheses include (1) elevated blood pressure, (2) abnormal vascular remodeling, (3) inhibition of protective mechanisms against ischemia-reperfusion injury, and (4) inhibition of 15-epi-lipoxin production. Varying results in different experimental models may be related to the fact that COX-2 is involved in numerous cellular functions. Inhibiting COX-2 in inflammatory cells may have favorable effects, whereas in organs such as the heart and brain and/or blood vessels may have deleterious effects. Currently, the "selective COX-2 inhibitors" are not selective in the sense that they inhibit COX-2 in all tissues without predilection to inflammatory cells and, as a result, may summate to increase the risk of cardiovascular events.

Original languageEnglish (US)
Pages (from-to)98-111
Number of pages14
JournalJournal of Cardiovascular Pharmacology and Therapeutics
Issue number2
StatePublished - Jun 2007
Externally publishedYes


  • Cardiovascular disease
  • Cycloxygenase-2 (COX-2)
  • Inflammation
  • Nonsteroidal antiinflammatory drugs

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine
  • Pharmacology (medical)


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