N-6 Polyunsaturated fatty acid oxidation increase oxidative stress, endothelial dysfunction and atherosclerosis in ApoE mice fed with chronic Western diet. Prevention strategy by apple polyphenols

Abstract

Atherosclerosis is a leading cause of mortality associated with endothelial dysfunction, oxidative stress and inflammation. One of the main risk factors is a Western diet rich in n-6 polyunsaturated fatty acids (n-6PUFA) which are sensitive to oxidation by heme iron of red meat in the gastrointestinal tract. This oxidation may increase 4-hydroxy-2-nonenal (4-HNE) formation, a cytotoxic aldehyde generated from n-6PUFA. Moreover, coupling of 4-HNE to LDL can lead to endothelial dysfunction and atherosclerosis development. By contrast, a diet rich in proanthocyanidins (PCs) (polyphenols, flavonoid class) is known to reduce oxidative stress as well as coronary artery disease. Evaluate chronic in Western diet effects and the potential protective capacity of PCs on vascular function and atherosclerosis development in an ApoE-/- mouse model. ApoE-/- mice were fed with: high-fat/red meat (HF-RM); HF-RM + n-6PUFA; HF-RM + n-6PUFA supplemented with apple puree or a phenolic extract (0.06% w/w) for 12 weeks. We reported an increase in fecal 4-HNE formation associated with a rise in plasmatic 4-HNE and oxLDL concentrations in n-6PUFA group. Moreover, adding oxidizable n-6PUFA to high fat diet was associated with ROS production (anion superoxide), worsened endothelial dysfunction, blood pressure and atheromatous plaque formation (136 vs. 166mm 2 in HF-RM). However, necrotic core size, fibrosis and lipid accumulation in atheromatous plaque were not affected. Interestingly, both polyphenol supplementations prevented the exacerbation of oxidative stress, endothelial dysfunction and atherosclerosis impairments as well as an increase in eNOS activity ( Table 1 ). Apple polyphenols limit the formation of absorbable 4-HNE during digestion and consequently protect vascular integrity against the damages of oxidative stress. Consumption of PC-rich fruits should thus be encouraged within the Western diet.