Reduced Progression of Atherosclerosis in Apolipoprotein E–Deficient Mice Following Consumption of Red Wine, or Its Polyphenols Quercetin or Catechin, Is Associated With Reduced Susceptibility of LDL to Oxidation and Aggregation

Abstract

The effect of consuming red wine, or its major polyphenol constituents catechin or quercetin, on the development of atherosclerotic lesions, in relation to the susceptibility of plasma LDL to oxidation and to aggregation, was studied in atherosclerotic apolipoprotein E deficient (E degree) mice. Forty E degree mice at the age of 4 weeks were divided into four groups, 10 mice in each group, and were supplemented for up to 6 weeks in their drinking water with placebo (1.1% alcohol); catechin or quercetin (50 micrograms/d per mouse), or red wine (0.5 mL/d per mouse). Consumption of catechin, quercetin, or red wine had no effect on plasma LDL or HDL cholesterol levels. The atherosclerotic lesion area was smaller in the treated mice by 39%, 46%, and 48%, respectively, in comparison with E degree mice that were treated with placebo. In accordance with these findings, cellular uptake of LDL derived after catechin, quercetin, or red wine consumption was found to be reduced by 31%, 40%, and 52%, respectively. These results were associated with reduced susceptibility to oxidation (induced by different modes such as copper ions, free radical generator, or macrophages) of LDL isolated after red wine or quercetin and, to a lesser extent after catechin consumption, in comparison with LDL isolated from the placebo group. Similar results were obtained when LDL was preincubated in vitro with red wine or with the polyphenols prior to its oxidation. Even in the basal oxidative state (not induced oxidation), LDL isolated from E degree mice that consumed catechin, quercetin, or red wine for 2 weeks was found to be less oxidized in comparison with LDL isolated from E degree mice that received placebo, as evidenced by 39%, 48%, and 49% reduced content of LDL-associated lipid peroxides, respectively. This effect could be related to enhanced serum paraoxonase activity in the polyphenol-treated mice. LDL oxidation was previously shown to lead to its aggregation. The present study demonstrated that the susceptibility of LDL to aggregation was reduced in comparison with placebo-treated mice, by 63%, 48%, or 50% by catechin, quercetin, and red wine consumption, respectively, and this effect could be shown also in vitro. The inhibition of LDL oxidation by polyphenols could be related, at least in part, to a direct effect of the polyphenols on the LDL, since both quercetin and catechin were found to bind to the LDL particle via the formation of an ether bond. We thus conclude that dietary consumption by E degree mice of red wine or its polyphenolic flavonoids quercetin and, to a lesser extent, catechin leads to attenuation in the development of the atherosclerotic lesion, and this effect is associated with reduced susceptibility of their LDL to oxidation and aggregation.

Compostos fenólicos e capacidade antioxidante de cultivares de uvas Vitis labrusca L. e Vitis vinifera L.

“…Catequinas e epicatequinas, por exemplo, têm demonstrado alta capacidade antioxidante e inibição da proliferação celular 12,26 . Há ainda evidências de que a ingestão de flavonóides como a quercetina e a catequina está associada à redução da oxidação do LDL e à redução da agregação plaquetária, contribuindo para a diminuição da progressão da lesão aterosclerótica 16 . O conteúdo de flavanóis (catequina e epicatequina), no presente estudo, variou entre 3,8 ± 0,1 e 61 ± 2 mg.100 g -1 .…”

Dose-dependent deleterious and salutary actions of the Nrf2 inducer dh404 in chronic kidney disease

“…Activation of these pathways confers protection by up-regulating expression of antioxidant enzymes, detoxifying compounds, protein chaperones, and trophic factors. In fact these phytochemicals have been shown to prevent or ameliorate a variety of diseases including cardiovascular disease [42,43], neurodegenerative disorders [44][45][46][47][48][49], and acute and chronic kidney disease [19][20][21][22][23]. In contrast, excessive or unrestrained activity of Nrf2 system has been shown to have adverse consequences.…”

Chronic senolytic treatment alleviates established vasomotor dysfunction in aged or atherosclerotic mice

“…These changes in plaque morphology are consistent, however, with previous reports demonstrating that senescent cells and cells overexpressing genes associated with progeroid syndromes have greater propensity to undergo osteogenic differentiation in vitro (Roos et al ., 2013). Critically, unlike previous studies leveraging chronic treatment with compounds such as quercetin (e.g., administered in drinking water) (Hayek et al ., 1997; Shen et al ., 2013), our study shows that weekly, intermittent treatment is sufficient to elicit lasting molecular and functional consequences in the vasculature of hypercholesterolemic mice. Altogether, we believe these observations lay the groundwork for future studies aimed at understanding effects of senolytics on plaque composition and stability both in isolation and as a complementary therapy to lipid‐lowering strategies.…”