Inhibition of vein graft intimal thickening by eicosapentanoic acid: Reduced thromboxane production without change in lipoprotein levels or low-density lipoprotein receptor density

Abstract

Marine lipids containing omega-3 fatty acids (chiefly, eicosapentanoic acid [EPA] and docosahexanoic acid [DHA]) may inhibit the development of atherosclerotic vascular disease, but the mechanisms responsible for this putative beneficial effect are unknown. We investigated the effects of EPA and DHA in a canine model of accelerated vein graft arteriosclerosis during a 3-month period. Twenty-five dogs were divided into three dietary groups: group I (control), group II (2.5% cholesterol), and group III (2.5% cholesterol plus 2 gm EPA/day [as MaxEPA]). The effects of EPA on vein graft intimal thickening, platelet and vascular prostaglandin metabolism, lipid and lipoprotein receptor metabolism, and hematologic parameters were assessed. Cholesterol feeding caused a significant 54% increase in graft intimal thickness compared with control animals (124.9 +/- 50.4 vs 81.2 +/- 32.4 micron; p = 0.013), which was prevented by supplementation with EPA in group III (56.9 +/- 30.0 micron; p = 0.001 vs group II). Intimal thickness in group III was not significantly different from that of control. EPA supplementation was also associated with a 38% decline in serum thromboxane levels from 457.0 +/- 129.3 pg/0.1 ml in group II to 283.5 +/- 96.9 pg/0.1 ml in group III (p = 0.007). The alterations in lipoprotein metabolism associated with cholesterol feeding were not affected by EPA: in both groups II and III, serum cholesterol and high-density lipoproteins and liver cholesterol content were elevated and hepatic low-density lipoproteins (LDL) receptor content was reduced. There were no differences between the three groups in terms of vein graft or native vessel prostacyclin production, hematocrit, platelet count, or coagulation parameters. In this canine model, dietary supplementation with marine omega-3 fatty acids reduced the extent and magnitude of accelerated vein graft intimal thickening induced by hypercholesterolemia; moreover, this beneficial effect was associated with lower serum thromboxane production and appeared to be independent of alterations in lipoprotein metabolism or LDL receptor density.

Eicosapentaenoic Acid, Arachidonic Acid and Eicosanoid Metabolism in Juvenile Barramundi Lates calcarifer

“…Although it is an unlikely real-world scenario to include high levels of any one LC-PUFA, these observations and those of a previous study, confirm that there are no growth stimulatory effects owing to any individual LC-PUFA in juvenile barramundi (Glencross and Rutherford, 2011). In many species, EPA can exert cardio-protective benefits such as lowering triglycerides and low-density lipoprotein levels (Aarsland et al, 1990;Cahill et al, 1988;Cottin et al, 2011;Wei and Jacobson, 2011;Weiner et al, 1986). Whereas ARA on the other hand, is an essential and necessary precursor to the 2-series and 4-series eicosanoids that mediate homeostasis during times of environmental or physiological stress (Bell and Sargent, 2003).…”

Omega‐3 Fatty Acids for the Prevention of Myocardial Infarction and Arrhythmias

“…Reiner et al reported a reduction of aortic atherosclerosis in mice with saturated fat diet supplemented with n-3 PUFA, and attributed it to the modulation of the expression and secretion of several macrophage effector molecules [7]. Other studies confirmed the reduction of atherogenesis in rodents and dog models of hypercholesterolemia or vascular injury subjected to fish oil rich diet, and highlighted the positive modulation of platelet function as a possible mechanism of action of n-3 PUFA [8][9][10][11].…”

Fish oil and the prevention and regression of atherosclerosis

“…Table 5 lists the studies exploring the effects of fish oil on allo-or autografted veins and arteries. The studies on arterialized venous [78][79][80] or synthetic [81] grafts are uniform in their outcome: fish oil reduces the extent of accelerated graft intimal proliferation, while not reducing the hypercholesteremia. All studies used dogs, added the fish oil as a supplement to the diet and measure intireal thickness of the graft or used a histologic grading system for intimal thickness, but only the dose of fish oil and the duration of the study varied.…”

“…After 6 weeks graft intimal thickness of the non-treated hypercholesterolemic animals averages 39 ~Lm versus 24 txm (240 mg 20 : 5n-3/kg/day) and 23 ~Lm (480 mg 20 : 5n-3/ kg/day) in the fish oil treated groups [79], demonstrating the lack of dose-dependency. After 3 months graft intimal proliferation of the control group is markedly higher (125 ~m [80] and 143 ~Lm [78]) and the effect of fish oil somewhat greater (54% decrease [80] and 46% decrease [78]). In the study by Casali et al [81] no data on intimal thickening are presented, but the authors state that there was a significant reduction (p < 0.04) in the fish oil treated normocholesterolemic animals.…”