Dietary eicosapentaenoic acid and docosahexaenoic acid from fish oil. Their incorporation into advanced human atherosclerotic plaques.

Abstract

The incorporation of fatty acids from dietary fish oil was measured in obstructive atherosclerotic plaques removed from 11 patients fed fish oil, rich in &>-3 fatty acids, for 6-120 days before a planned arterial endarterectomy. The fatty acids of plasma and atheroma were analyzed with special reference to docosahexaenoic acid (DHA, 22:6) and eicosapentaenoic acid (EPA, 20:5), the principal &>-3 fatty acids offish oil. The o>-3 fatty acid content increased greatly in plasma from 0.9% of fatty acids to 14.8% in cholesteryl esters, from 3.8% to 22.1% in phospholipids, and from 1.3% to 21.9% in triglycerides. The to-3 fatty acid content of the atherosclerotic plaques was also greater when compared with that of plaques removed from 18 non-fish oil-fed controls. The &>-3 fatty acid in cholesteryl esters of the plaques was 4.9% in the experimental group versus 1.4% in control plaque, in phospholipids it was 8.8% versus 1.8%, and in triglycerides it was 4.7% versus 0.7% (p<0.001 for each lipid class). The two major co-3 fatty acids (DHA and EPA) behaved differently. Compared with their respective plasma levels, relatively more DHA than EPA was deposited into the plaques. Whereas the increase of eo-3 fatty acids in plasma reached a plateau 3 weeks after initiation of fish oil feeding, a linear increase in plaque to-3 fatty acids continued with time. As a result of the changes in fatty acid composition, the lipid classes of both plasma and plaque had a higher unsaturation index in the fish oil-fed group. Our data demonstrate that dietary to-3 fatty acids are readily incorporated into advanced human atherosclerotic plaques. Changes in the fatty acids of plasma lipids are reflected in substantial changes in the plaque fatty acid content over a relatively short time. Because <w-3 fatty acids affect so many factors predisposing to both thrombosis and atherosclerosis, these data may have clinical implications. (Arteriosclerosis

Ratio of Serum n-3 to n-6 Polyunsaturated Fatty Acids and the Incidence of Major Adverse Cardiac Events in Patients Undergoing Percutaneous Coronary Intervention

“…Rapp et al found substantial incorporation of EPA and DHA into plaque lipids following consumption of a very high dose of fish oil (48-64 g/day providing 16-21 g EPA + DHA/day). 31 In contrast, 2 other studies using considerably lower doses of EPA and DHA (0.81 g EPA and 0.675 g DHA/day) found significantly higher levels of EPA in atherosclerotic plaques than DHA. 26,32 Moreover, plaques from patients treated with fish oil had fewer thin fibrous caps and signs of inflammation, with more plaques containing thick fibrous caps, no signs of inflammation, 26 and lower levels of inflammatory agents and mRNA for matrix metalloproteinases (MMP-7 and -12), interleukin-6, and intercellular adhesion molecules.…”

N-3 polyunsaturated fatty acids modulate the expression of functionally associated molecules on human monocytes and inhibit antigen presentation in vitro

“…Supplementation studies have shown that EPA and DHA are incorporated into the lipids of advanced atherosclerotic plaques in man [24], and it is possible that a reduced expression of MHC class II molecules might inhibit the antigen-presenting function of the local macrophages, thereby prolonging, if not preventing, lesion development.…”

Novel Docosatrienes and 17S-Resolvins Generated from Docosahexaenoic Acid in Murine Brain, Human Blood, and Glial Cells

“…Media were removed from semiconfluent monolayers (ϳ75%) and replaced with Hanks' buffer (37°C, 10 ml) containing HEPES, 10 mM, pH 7.4, and [1-14 C]DHA (55 mCi/mmol, American Radiolabeled Chemicals, Inc., 10 M), or unlabeled C22:6 (ϳ10 M, Oxford Biomedical Research) was added in EtOH (5-10 l). Cells were placed in an incubator with an atmosphere of 5% CO 2 at 37°C for 90 min, and aliquots (100 l) were removed at 30-min intervals and analyzed by scintillation counting to determine cellular [1][2][3][4][5][6][7][8][9][10][11][12][13][14] C]DHA. At 90 min, buffer was removed and cells were washed with Hanks' buffer (10 ml, 37°C).…”