Digestive n-6 Lipid Oxidation, a Key Trigger of Vascular Dysfunction and Atherosclerosis in the Western Diet: Protective Effects of Apple Polyphenols

Scope: A main risk factor of atherosclerosis is a Western diet (WD) rich in n-6 polyunsaturated fatty acids (PUFAs) sensitive to oxidation. Their oxidation can be initiated by heme iron of red meat leading to the formation of 4-hydroxy-2-nonenal (4-HNE), a cytotoxic aldehyde. An increased 4-HNE production is implicated in endothelial dysfunction and atherosclerosis. By contrast, a diet rich in proanthocyanidins reduces oxidative stress and arterial diseases. This study evaluates the effects of a WD on vascular integrity in ApolipoproteinE (ApoE−/−) mice and the protective capacity of apple extract and puree rich in antioxidant proanthocyanidins. Methods and results: ApoE-/- mice are fed during 12 weeks with a WD with or without n-6 PUFAs. Moreover, two WD + n-6 PUFAs groups are supplemented with apple puree or phenolic extract. An increase in digestive 4-HNE production associated with a rise in plasmatic 4-HNE and oxidized LDL concentrations is reported. Oxidizable n-6 PUFAs consumption is associated with a worsened endothelial dysfunction and atherosclerosis. Interestingly, supplementations with apple polyphenol extract or puree prevented these impairments while reducing oxidative stress. Conclusion: n-6 lipid oxidation during digestion may be a key factor of vascular impairments. Nevertheless, an antioxidant strategy can limit 4-HNE formation during digestion and thus durably protect vascular function.