Effects of dietary flaxseed on vascular contractile function and atherosclerosis during prolonged hypercholesterolemia in rabbits

Abstract

-Dietary flaxseed has significant anti-atherogenic effects. However, the limits of this action and its effects on vascular contractile function are not known. We evaluated the effects of flaxseed supplementation on atherosclerosis and vascular function under prolonged hypercholesterolemic conditions in New Zealand White rabbits assigned to one of four groups for 6, 8, or 16 wk of feeding: regular diet (RG), 10% flaxseed-supplemented diet (FX), 0.5% cholesterol-supplemented diet (CH), and 0.5% cholesterol-and 10% flaxseed-supplemented diet (CF). Cholesterol feeding resulted in elevated plasma cholesterol levels and the development of atherosclerosis. The CF group had significantly less atherosclerotic lesions in the aorta and carotid arteries after 6 and 8 wk than the CH animals. However, the antiatherogenic effect of flaxseed supplementation was completely attenuated by 16 wk. Maximal tension induced in aortic rings either by KCl or norepinephrine was not impaired by dietary cholesterol until 16 wk. This functional impairment was not prevented by including flaxseed in the high-cholesterol diet. Aortic rings from the cholesterol-fed rabbits exhibited an impaired relaxation response to acetylcholine at all time points examined. Including flaxseed in the high-cholesterol diet completely normalized the relaxation response at 6 and 8 wk and partially restored it at 16 wk. No significant changes in the relaxation response induced by sodium nitroprusside were observed in any of the groups. In summary, dietary flaxseed is a valuable strategy to limit cholesterol-induced atherogenesis as well as abnormalities in endothelial-dependent vasorelaxation. However, these beneficial effects were attenuated during prolonged hypercholesterolemic conditions. linseed; acetylcholine; nutrition; polyunsaturated fatty acids; vascular relaxation ATHEROSCLEROSIS IS THE leading cause of cardiovascular morbidity and mortality in North America (77). Atherosclerosis induces two significant pathological processes: an ischemic event due to blood flow obstruction and vascular contractile dysfunction. It is well known that atherosclerosis is associated with elevated circulating cholesterol levels. Elevated plasma cholesterol concentrations induced by cholesterol feeding result in the development of atherosclerosis and an impairment in endothelium-dependent vasodilation in rabbits (9,26,29,30,36). The development of interventions to inhibit cholesterolinduced atherosclerosis and the associated vascular dysfunction have received much attention because of this strong association. For example, there is an increasing interest in nutritional interventions that may prevent the development of atherosclerosis and protect against the vascular function abnormalities induced by cholesterol consumption. Flaxseed is one such novel dietary intervention. Flaxseed is a good source of soluble and insoluble dietary fiber and is the richest plant source of ␣-linolenic acid [ALA; C18:3 n-3, omega-3 (n-3) fatty acid] as well as the lignan secoisolariciresinol digluco...

Bioavailability of α-linolenic acid from flaxseed diets as a function of the age of the subject

“…Plasma fatty acids were measured by gas chromatography as described in detail elsewhere (Dupasquier et al, 2006(Dupasquier et al, , 2007. Briefly, blood samples were centrifuged at 1800  g for 5 min at 4 1C to obtain plasma, and then the plasma fatty acids were derived and then analyzed using a Varian CP-3800 gas chromatograph (Varian Inc., Palo Alto, CA, USA), equipped with a flame ionization detector and Varian CP-Sil 88 capillary column (Varian; 60 m  0.25 mm  0.20 mm).…”

“…C17:0 was used as the internal standard and the fatty acid contents of the sample were identified by comparison with an authentic standard, GLC-462 (Nu-Chek Prep, Elysian, MN, USA). Plasma cholesterol and triglyceride (TG) levels were measured as described (Dupasquier et al, 2006(Dupasquier et al, , 2007.…”

“…However, clinical trials to prove this have not been attempted to date. In experimental work, dietary flaxseed has shown anti-arrhythmic (Ander et al, 2004) and anti-atherogenic actions (Dupasquier et al, 2006(Dupasquier et al, , 2007. This would suggest that initiating a larger clinical trial to investigate the cardiovascular benefits of dietary flaxseed is warranted.…”

Effects of dietary flaxseed on atherosclerotic plaque regression

“…Unlike drug therapy, n-3 PUFAs have fewer and milder side effects and are generally considered safe (37). Moreover, milled flaxseed has proven to be cardioprotective and antiatherogenic in animal models (7,22,23,44) as well as in clinical settings (50). However, although flaxseed can diminish the progression of atherosclerotic plaques, it is unclear if dietary supplementation with flaxseed can regress established atherosclerotic plaques.…”

A comparison of the effects of fish oil and flaxseed oil on cardiac allograft chronic rejection in rats

“…Although the biological effects of ALA may not be the same as those for EPA and DHA, we have recently demonstrated that flaxseed products exhibit antiatherosclerotic activities in cholesterol-fed rabbits and LDL-receptor knockout (KO) mice (10,11). The mechanisms underlying these beneficial properties of flaxseed may be mediated through its beneficial effects on lipid metabolism, platelet function, inflammation, endothelial cell function, and arrhythmia (36).…”