Therapeutic impact of eicosanoids in atherosclerotic disease

Abstract

Polyunsaturated fatty acid (PUFA) components of the diet, especially of the omega-3 variety, protect against atherosclerosis and its related thrombotic complications. Mechanisms involved probably involve the eicosanoids. Classic PGE1 has now found a role in the treatment of peripheral vascular disease. Prostacyclin (PGI2) discovered over ten years ago has also been introduced into clinical medicine; orally active analogs are being introduced with clinical potential in a variety of atherosclerotic and thrombotic disorders. "Endothelium-derived relaxing factor (EDRF)" has been identified with nitric oxide, an active metabolite of the classic nitrodilator compounds, which (like NO itself) is synergistic with prostacyclins in inhibition of platelet activation, but without similar synergistic effects on vasodilation. This finding is of considerable importance both from physiological and therapeutic standpoints. The therapeutic efficacy of acetylsalicylic acid (ASA, aspirin) in the secondary prevention of myocardial infarction is now established. For primary prevention, it is probably inferior to diet (e.g. fish oil) and lifestyle changes due to increased incidence of cerebrovascular bleeding. The unfulfilled therapeutic promise of thromboxane synthesis inhibitors may be overcome by introduction of dual TX receptor/synthesis inhibitors. Recent advances suggest that PGE1, prostacyclin analogs and high dose fish oil could act beneficially against background nitrodilator therapy in preventing thrombosis and mitogen-stimulated restenosis following thrombolytic or surgical treatment of coronary artery occlusion.