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CICLOOXIGENASA 2: ¿UNA NUEVA DIANA TERAPEUTICA EN LA ATEROSCLEROSIS

(especial para SIIC © Derechos reservados)
La ciclooxigenasa 2 (COX-2), una enzima clave en la generación de prostaglandinas proinflamatorias, como PGE2, parece jugar un papel importante en diversas fases de la aterosclerosis. Resultados recientes de nuestro grupo indican que puede, asimismo, constituir un marcador no invasivo de riesgo aterosclerótico, al haberse detectado incremento de PGE2 en relación con los marcadores tradicionales de riesgo aterosclerótico y con el espesor íntima-media de la carótida, un marcador no invasivo de aterosclerosis subclínica. La posibilidad de modular la actividad de COX-2, o de prostaglandinas derivadas de su efecto, puede representar una nueva alternativa en la prevención y tratamiento de la aterosclerosis. Sin embargo, existe controversia sobre el empleo de inhibidores electivos de COX-2 por su posible riesgo cardiovascular.
paramo9.jpg Autor:
José a. Páramo
Columnista Experto de SIIC

Institución:
Laboratorio de Aterosclerosis, Centro para la Investigación Médica Aplicada (CIMA)

Artículos publicados por José a. Páramo
Recepción del artículo
24 de Noviembre, 2005 		Aprobación
3 de Enero, 2006
Primera edición
24 de Abril, 2006 		Segunda edición, ampliada y corregida
7 de Junio, 2021

CICLOOXIGENASA 2: ¿UNA NUEVA DIANA TERAPEUTICA EN LA ATEROSCLEROSIS

Resumen
En la actualidad se acepta que la aterosclerosis es un proceso inflamatorio crónico de la pared arterial asociado con la presencia de diversos factores de riesgo. Desde las fases iniciales hasta la ruptura de una placa aterosclerótica vulnerable, un estado de “microinflamación vascular” juega un papel fisiopatológico relevante. Diversos marcadores inflamatorios (CRP, citocinas, moléculas de adhesión), demostraron un papel importante en este proceso inflamatorio. Evidencias clínicas y experimentales también indican que la ciclooxigenasa 2 (COX-2), una enzima que cataliza la generación de prostaglandinas a partir del ácido araquidónico, también contribuye al desarrollo de la lesión aterosclerótica. Nuestro grupo demostró recientemente asociación de PGE2, un metabolito derivado de COX-2 en monocitos, con factores de riesgo y espesor íntima-media de la carótida en un grupo de sujetos asintomáticos, lo que sugiere que la vía COX-2/PGE2 podría jugar un papel en la aterosclerosis y representar una nueva diana terapéutica. Desde el punto de vista teórico, los inhibidores selectivos de la COX-2, denominados genéricamente coxibs (celecoxib, rofecoxib, valdecoxib, lumiracoxib, etc.), podrían ser útiles como fármacos antiinflamatorios en este proceso, sin los efectos secundarios de la aspirina u otros antiinflamatorios no esteroides. Sin embargo, diversos estudios clínicos sugieren que pueden inducir una aumento de complicaciones cardiovasculares, por alteración del equilibrio tromboxano/prostaciclina, por lo que su uso debe restringirse, especialmente en pacientes con alto riesgo aterosclerótico.

Palabras clave
Ciclooxigenasa 2, aterotrombosis, prostaglandina E2, inflamación, coxibs, riesgo cardiovascular


Artículo completo
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CYCLOOXYGENASE-2: A NEW THERAPEUTIC TARGET IN ATHEROSCLEROSIS

Abstract
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 called microinflammation, appears to play a key pathogenetic role. Systemic inflammatory markers (CRP, cytokines adhesion moleculaes) 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 PGE2 in relation to cardiovascular risk factors and subclinical atherosclerosis in asymptomatic subjects. Our findings support the notion that the COX-2/PGE2 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.), might be a promise as anti-inflammatory drugs without some of the side effects of aspirin or non steroidal antiinflammatory agents. However, clinical studies raise several clinically relevant questions in reference to their beneficial role in atherosclerosis prevention. Because of increased thrombogenicity and cardiovascular risk, coxibs should be restricted in atherosclerosis-prone patients.

Key words
Cyclooxygenase-2, atherothrombosis, prostaglandin E2, inflammation, coxibs, cardiovascular risk

Clasificación en siicsalud
Artículos originales > Expertos de Iberoamérica >
página   www.siicsalud.com/des/expertocompleto.php/

Especialidades
Principal: Cardiología
Relacionadas: Bioquímica, Diagnóstico por Laboratorio, Farmacología, Medicina Farmacéutica, Medicina Interna



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