The cycloxygenase 2 (COX-2) story: it's time to explain, not inflame.
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.
Salinas
Guillermo
G
Division of Cardiology, Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas 77555-0553, USA.
Rangasetty
Umamahesh C
UC
Uretsky
Barry F
BF
Birnbaum
Yochai
Y
D050197:Atherosclerosis / Q000188:drug therapy / Q000503:physiopathology; D002318:Cardiovascular Diseases / Q000139:chemically induced*; D002986:Clinical Trials as Topic; D003324:Coronary Artery Disease / Q000188:drug therapy / Q000503:physiopathology; D051546:Cyclooxygenase 2 / Q000502:physiology*; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000503:physiopathology; D015398:Signal Transduction; D013927:Thrombosis / Q000139:chemically induced
D052246:Cyclooxygenase 2 Inhibitors; D051546:Cyclooxygenase 2