Thrombosis eicosanoids

As noted above, eicosanoids are involved in thrombosis because TXA2 promotes platelet aggregation and PGI2 inhibits it. Aspirin inhibits platelet COX to produce a mild clotting defect. 

Omega-3 fatty acids are long-chain polyunsaturated fatty acids. The parent fatty acid of this group is alpha-linolenic acid, an essential fatty acid that the body is unable to synthesize alpha-linolenic acid can be converted in the body to eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). In animals and man, these acids reduce the production of several compounds that are involved in inflammation and thrombosis, such as eicosanoids (prostaglandins, thromboxanes, prostacyclin, and leukotrienes) and cytokines (interleukin II-l) (1). The extent of the conversion of alpha-linolenic acid to EPA and DHA is unclear. The conversion process appears to be inhibited by a high intake of linoleic acid, another essential fatty acid (2). In addition, alpha-linolenic acid is found in dark green vegetables and the oils of certain nuts and seeds, especially rape seeds and soya beans. 

Figure 13.12. Metabolic pathways for the formation of oxidized lipoproteins and eicosanoids. These oxidation products contribute to atherogenesis, thrombosis and immune suppression.

High intakes of the long-chain CO-3 polyunsaturated fatty acids (as found in fish oils) may additionally provide protection against thrombosis, as they form the 3-series eicosanoids, which inhibit platelet cohesiveness. 

Of the long-chain n-3 fatty acids, DHA is important in maintaining normal cerebral cortex and other neuro-related tissues and is essential for functions of the retina. EPA is an eicosanoid precursor, yielding products which reduce platelet aggregation and the risk of arterial thrombosis, among other functions. Stearidonic acid is an essential, but less investigated, intermediary metabolite in the biosynthesis of EPA and DHA in humans. 

Eicosanoids Relevance to Endothelial Function, Thrombosis, infiammation, and Atheroscierosis... 

The available evidence suggests that n-6 fatty acid-derived eicosanoids are generally proinflamma-tory and prothrombotic. In contrast, eicosanoids derived from n-3 fatty acids have attenuated biological activity on cardiovascular risk factors. The effects of altering n-6 PUFA intake, in conjvmction with changes in other polyunsaturated fatty acids, as well as other classes of fatty acids, on endothelial function, thrombosis, and inflammation are not understood. The relative proportion of all the classes of fatty acids in the diet may well be more important and relevant to cardiovascular risk reduction than any single class of fatty acids. Clearly such research warrants further investigation. 

---