Apple polyphenols decrease endothelial dysfunction and atherosclerosis after chronic Western diet in a ApoE mouse model

Abstract

Atherosclerosis is a multifactorial disease and a leading cause of mortality in industrialized countries associated with endothelial dysfunction, oxidative stress and inflammation, which contribute to lesion formation, plaque rupture and thrombosis. One of the main risk factors for this pathology is the pro-oxidant Western diet rich in ω-6 polyunsaturated fatty acids (ω-6PUFA) which are sensitive to oxidation by heme iron of red meat in the gastrointestinal tract. This oxidation may increase the 4-hydroxy-2-nonenal (4-HNE) formation, a specific genotoxic and cytotoxic aldehyde generated from ω-6PUFA. Moreover, coupling of 4-HNE to LDL is a key step in atherosclerosis development. By contrast, a diet rich in procyanidins (PCs) (polyphenols, flavonoid) is known to reduce oxidative stress as well as coronary artery disease. Evaluate chronic pro-oxidant Western diet effects on atherosclerosis development and vascular function in an ApoE −/− mice model and the potential antioxidant capacity of PCs. ApoE −/− mice were fed with: high-fat/red meat; high-fat/ω-6PUFA/red meat; high-fat/ω-6PUFA/red meat supplemented with apple puree (0.06% eq. polyphenols) or a phenolic extract for 12 weeks. No difference was evidenced regarding insulin resistance or obesity development. However, we observed that lipid oxidation worsens endothelial dysfunction (62% vs. 75% maximal relaxation) compared to the high-fat diet rich in saturated fatty acids. This alteration of the endothelium was associated with an increase of arterial pressure and atheromatous plaque formation (136 mm 2 vs. 166 mm 2 ). Interestingly, both polyphenol supplementations prevented the exacerbation of endothelial function and atherosclerosis impairments. Apple PCs may limit the formation of absorbable lipid oxidation products such as 4-HNE during digestion and consequently protect vascular function. The reintroduction of PC-rich fruits into our diet could have a health benefit.