Cyclooxygenase isoforms and atherosclerosis.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used in the treatment of arthritis and pain. However, their long-term use is limited by gastrointestinal (GI) side effects such as gastric ulcers. NSAIDs act by inhibiting an enzyme called cyclooxygenase. Cyclooxygenase (COX) catalyses the generation of prostaglandins from arachidonic acid. Two isoforms of the enzyme exist--COX-1 and COX-2--both of which are targets for NSAIDs. Although they are associated with GI toxicity, NSAIDs have important antithrombotic and anti-inflammatory effects. The GI injury has been attributed to COX-1 inhibition and the anti-inflammatory effects to COX-2 inhibition. As COX-2 is traditionally viewed as an inducible enzyme, selective inhibition of COX-2 by 'coxibs' (selective COX-2 inhibitors) has been employed to achieve anti-inflammatory and analgesic effects without GI side effects. However, recently there have been suggestions that chronic administration of coxibs might increase the risk of cardiovascular events, such as atherosclerosis, compared with traditional NSAIDs. In vascular disease, there is increased expression of both COX-1 and COX-2, resulting in enhanced prostaglandin generation. The specific role of COX-1 and COX-2 in vascular regulation is still unknown but such knowledge is essential for the effective use of coxibs. Although more evidence is pointing to selective COX-1 inhibition as a therapeutic measure in inflammatory atherosclerosis, there are some studies that suggest that inhibition of COX-2 might have a potential benefit on atherosclerosis.
Belton
Orina
O
Department of Clinical Pharmacology, Royal College of Surgeons in Ireland, 123 St Stephens Green, Dublin 2, Ireland. obelton@rcsi.ie
Fitzgerald
Desmond J
DJ
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D050197:Atherosclerosis / Q000188:drug therapy*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D005767:Gastrointestinal Diseases / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D007527:Isoenzymes; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D011451:Prostaglandin-Endoperoxide Synthases