Dietary flaxseed inhibits atherosclerosis in the LDL receptor-deficient mouse in part through antiproliferative and anti-inflammatory actions

Abstract

Dietary flaxseed has been shown to have potent antiatherogenic effects in rabbits. The purpose of the present study was to investigate the antiatherogenic capacity of flaxseed in an animal model that more closely represents the human atherosclerotic condition, the LDL receptor-deficient mouse (LDLrKO), and to identify the cellular mechanisms for these effects. LDLrKO mice were administered a regular diet (RG), a 10% flaxseed-supplemented diet (FX), or an atherogenic diet containing 2% cholesterol alone (CH) or supplemented with 10% flaxseed (CF), 5% flaxseed (CF5), 1% flaxseed (CF1), or 5% coconut oil (CS) for 24 wk. LDLrKO mice fed a cholesterol-supplemented diet exhibited a rise in plasma cholesterol without a change in triglycerides and an increase in atherosclerotic plaque formation. The CS mice exhibited elevated levels of plasma cholesterol, triglycerides, and saturated fatty acids and an increase in plaque development. Supplementation of the cholesterol-enriched diet with 10% (wt/wt) ground flaxseed lowered plasma cholesterol and saturated fatty acids, increased plasma ALA, and inhibited plaque formation in the aorta and aortic sinus compared with mice fed a diet supplemented with only dietary cholesterol. The expression of proliferating cell nuclear antigen (PCNA) and the inflammatory markers IL-6, mac-3, and VCAM-1 was increased in aortic tissue from CH and CS mice. This expression was significantly reduced or normalized when flaxseed was included in the diet. Our results demonstrate that dietary flaxseed can inhibit atherosclerosis in the LDLrKO mouse through a reduction of circulating cholesterol levels and, at a cellular level, via antiproliferative and anti-inflammatory actions.

Technological, physico-chemical and sensory properties of raw and cooked meat batter incorporated with various levels of cold milled flaxseed powder

“…Flaxseed has potential to reduce the risk of cardiovascular diseases and some cancers, particularly hormone dependent cancers such as prostate and breast cancer. It has been reported to act as anti-arrhythmic (Ander et al 2004), antiatherogenic (Dupasquier et al 2006;Dupasquier et al 2007), and anti-inflammatory (Dupasquier et al 2007) in addition to improving vascular function (Dupasquier et al 2006).…”

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

“…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.…”

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

“…Therefore, one may propose that both oils (fish and flaxseed) may have antiatherogenic properties, regardless of the type of n-3 FAs, through beneficial modifications in lipoprotein metabolism. It is interesting to note that we have observed a strong association between the amount of oil in dietary flaxseed and the degree of prevention of atherosclerosis in LDL-receptor KO mice (10). However, fish oil did not prevent atherosclerosis in apolipoprotein E-KO mice (54).…”

“…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).…”