Can COX-2 inhibitor-induced increase in cardiovascular disease risk be modified by essential fatty acids?
Article Details
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Das UN
Can COX-2 inhibitor-induced increase in cardiovascular disease risk be modified by essential fatty acids?
J Assoc Physicians India. 2005 Jul;53:623-7.
- PubMed ID
- 16190133 [ View in PubMed]
- Abstract
Selective COX-2 inhibitors increase the risk of myocardial infarction and stroke. This has been attributed to their ability to inhibit endothelial COX-2 derived prostacyclin (PGI2) but not platelet COX-1 derived thromboxane A2 (TXA2). On the other hand, aspirin blocks both COX-1 and COX-2 enzymes without decreasing PGI2 but blocks TXA2 synthesis that explains its beneficial action in the prevention of coronary heart disease (CHD). The inhibitory action of aspirin on COX-1 and COX-2 enzymes enhances the tissue concentrations of dihomo-gamma-linolenic acid (DGLA), arachidonic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). These fatty acids form precursors to PGE1, PGI2, PGI3, lipoxins (LXs), and resolvins that have anti-inflammatory actions. In contrast, increase in the concentrations of DGLA, AA, EPA, and DHA is much less with specific COX-2 inhibitors since they do not block the formation of eicosanoids through COX-1 pathway. COX-2 inhibitors interfere with the formation of LXs and resolvins that have neuroprotective and cardioprotective actions. EPA and PGI2 have anti-arrhythmic action. EPA, DHA, and AA augment eNO formation that prevents atherosclerosis. This suggests that COX-2 inhibitors increase cardiovascular and stroke risk by interfering with the formation of eNO, PGI2, LXs, and resolvins and implies that combining EFAs with COX-2 inhibitors could prevent these complications.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Dihomo-gamma-linolenic acid Prostaglandin G/H synthase 1 Protein Humans YesInhibitorDetails Dihomo-gamma-linolenic acid Prostaglandin G/H synthase 2 Protein Humans YesNot Available Details Icosapent Prostaglandin G/H synthase 1 Protein Humans YesInhibitorDetails Icosapent Prostaglandin G/H synthase 2 Protein Humans YesInhibitorDetails