[Cyclooxygenase-2: a new therapeutic target in atherosclerosis?].
It is now widely accepted that atherosclerosis is a complex chronic inflammatory disorder of the arterial tree associated with several risk factors. From the initial phases to eventual rupture of vulnerable atherosclerotic plaques, a low-grade inflammation, also termed microinflammation, appears to play a key pathogenetic role. Systemic inflammatory markers (C reactive protein, cytokines adhesion molecules) also play a role in this process. Experimental and clinical evidence suggests that cyclooxygenase-2 (COX-2), an enzyme which catalyzes the generation of prostaglandins from arachidonic acid, also contributes to lesion formation. Recent reports by our group have demonstrated increased monocyte COX-2 activity and the production of prostaglandin E2 in relation to cardiovascular risk factors and subclinical atherosclerosis in asymptomatic subjects. Our findings support the notion that the COX-2/prostaglandin E2 axis may have a role, raising the question as to whether its selective inhibition might be an attractive therapeutic target in atherosclerosis. COX-2 inhibitors, collectively called "coxibs" (celecoxib, rofecoxib, valdecoxib, lumiracoxib, etc), held a promise as anti-inflammatory drugs without the some of the side effects of aspirin or non steroidal antiinflammatory agents. However, clinical studies raise several clinically relevant questions as to their beneficial role in atherosclerosis prevention, because of increased thrombogenicity and cardiovascular risk, and therefore coxibs should be restricted in atherosclerosis-prone patients.
Páramo
José A
JA
Servicio de Hematología, Laboratorio de Aterosclerosis,Centro para la Investigación Médica Aplicada (CIMA), Clínica Universitaria,Universidad de Navarra, Pamplona, Navarra, España. japaramo@uav.es
Beloqui
Oscar
O
Orbe
Josune
J
D050197:Atherosclerosis / Q000188:drug therapy* / Q000201:enzymology*; D002319:Cardiovascular System / Q000187:drug effects / Q000201:enzymology; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D012306:Risk
D052246:Cyclooxygenase 2 Inhibitors; D051546:Cyclooxygenase 2