Apple polyphenols decrease endothelial dysfunction and atherosclerosis in ApoE mice fed with chronic Western diet

Abstract

Atherosclerosis is a leading cause of mortality in industrialized countries and is associated with endothelial dysfunction, oxidative stress and inflammation. One of the main risk factors is a pro-oxidant Western diet rich in ω-6 polyunsaturated fatty acids (ω-6 PUFA) 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 ω-6 PUFA. Moreover, coupling of 4-HNE to LDL is a key step in 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 pro-oxidant 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 + ω-6 PUFA; HF-RM + ω-6 PUFA 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 LDLox concentrations in ω-6 PUFA group. This increase was prevented by apple polyphenols supplementation. Moreover, adding oxidizable ω-6 PUFA to high fat diet worsens 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 endothelial dysfunction and atherosclerosis impairments which was associated with an increase in eNOS activity. Apple polyphenols limit the formation of absorbable lipid oxidation products during digestion (4-HNE) and consequently protect vascular integrity. Consumption of PC-rich fruits should thus be encouraged within the Western diet.