Can COX-2 inhibitor-induced increase in cardiovascular disease risk be modified by essential fatty acids?

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.

• Authors: U N Das
• Journal: The Journal of the Association of Physicians of India (J Assoc Physicians India) Vol. 53 Pg. 623-7 (Jul 2005) ISSN: 0004-5772 [Print] India
• PMID: 16190133 (Publication Type: Journal Article, Review)

Chemical References

• Cyclooxygenase Inhibitors
• Enzyme Inhibitors
• Fatty Acids, Essential

Topics

• Cardiovascular Diseases (chemically induced, metabolism, prevention & control)
• Cyclooxygenase Inhibitors (adverse effects)
• Enzyme Inhibitors (adverse effects)
• Fatty Acids, Essential (metabolism, therapeutic use)
• Humans
• Risk Factors