Oxidised plant sterols as well as oxycholesterol increase the proportion of severe atherosclerotic lesions in female LDL receptor^+/ −mice

Abstract

Oxysterols (oxidised cholesterol) may play a role in the pathogenesis of CVD. Similar to cholesterol, plant sterols are susceptible to oxidation. However, less is known about the potential atherogenicity of oxidised plant sterols (oxyphytosterols). In the present study, the atherogenicity of a mixture of oxyphytosterols was examined by feeding female LDL receptor-deficient (LDLR þ/2 ) mice for 35 weeks a control diet (atherogenic high-fat diet; n 9), an oxysterol diet (control diet þ 0·025 % (w/w) oxysterols; n 12) or an oxyphytosterol diet (control diet þ 0·025 % (w/w) oxyphytosterols; n 12). In the LDLR þ/2 mice, serum levels of cholesterol, lipoprotein profiles, cholesterol exposure and inflammatory markers at the end of the experiment were comparable between the three diet groups. Nevertheless, the proportion of severe atherosclerotic lesions was significantly higher after oxysterol (41 %; P¼ 0·004) and oxyphytosterol (34 %; P¼0·011) diet consumption than after control diet consumption (26 %). Oxyphytosterol levels in the lesions were the highest in the oxyphytosterol group. Here, we show that not only dietary oxysterols but also dietary oxyphytosterols increase the proportion of severe atherosclerotic lesions. This suggests that plant sterols when oxidised may increase atherosclerotic lesion severity instead of lowering the size and severity of lesions when fed in their non-oxidised form. Therefore, this finding might give an indication as to where to find the answer in the current hot debate about the potential atherogenicity of plant sterols. However, to what extent these results can be extrapolated to the human situation warrants further investigation. Key words: Diets: Oxysterols: Oxyphytosterols: Lipoproteins: Atherosclerosis Several lines of evidence suggest that oxysterols (oxidised cholesterol) are atherogenic and play a role in the pathogenesis of CVD. Plant sterols are structurally related to cholesterol (1) , and the presence of one or more unsaturated bonds also makes the plant sterols susceptible to oxidation. Only small amounts of oxidised plant sterols (oxyphytosterols) can be found in the diet (2,3) . Nevertheless, relatively high concentrations of oxyphytosterols are present in the serum of sitosterolaemic patients (4) and smaller amounts in the plasma of healthy individuals (5,6) . The fact that oxyphytosterol concentrations are high in sitosterolaemic patients, who also have severely elevated plasma plant sterol concentrations, may suggest that higher plasma plant sterol concentrations translate into higher plasma oxyphytosterol concentrations. Indeed, Husche et al. (6) have recently shown that consumption of a plant sterol-enriched margarine for 4 weeks increases serum 7b-OH-campesterol concentrations in healthy individuals. Factors that are related to the oxidative behaviour of plant sterols are unknown. For cholesterol, however, it has been suggested that patients characterised by oxidative stress such as type 2 diabetics (7) and patients with stable coronary artery disease (8)...

Unsaturated lipid matrices protect plant sterols from degradation during heating treatment

“…The hypothesis of their possible absorption into the organism through the diet is supported by several studies (Bang, Arakawa, Takada, Sato, & Imaizumi, 2008;Liang et al, 2011). Moreover, recent evidence in a mice model fed with a mixture of POPs, reinforced this hypothesis (Plat et al, 2014).…”

Phytosterol oxidation products in enriched foods: Occurrence, exposure, and biological effects

“…An in vivo study in apolipoprotein E-deficient mice could not establish a correlation between dietary administered POPs (0.2 g/kg diet) for nine weeks and serum cholesterol concentrations as well as the size of atherosclerotic plaques when compared to a phytosterol-supplemented diet (0.2 g/kg diet) [82]. A recent study by Plat et al [109] investigated the effects of a westernlike diet containing 0.25% cholesterol compared to the same diet in which 10% of the cholesterol had been replaced by cholesterol oxidation products or dietary POPs in LDL receptor +/− mice for 35 weeks. Concerning the lesion size, no differences could be observed among the three groups, confirming the results obtained by the above-mentioned study.…”

“…A recent study by Plat et al. investigated the effects of a western‐like diet containing 0.25% cholesterol compared to the same diet in which 10% of the cholesterol had been replaced by cholesterol oxidation products or dietary POPs in LDL receptor +/− mice for 35 weeks. Concerning the lesion size, no differences could be observed among the three groups, confirming the results obtained by the above‐mentioned study.…”

Vascular effects of oxysterols and oxyphytosterols in apoE −/− mice

“…Another approach is to feed oxyphytosterols, as has been done for oxysterols [13]. So far, there have been only limited data regarding the effects of an oxyphytosterol-enriched diet on atherogenesis, which was however suggestive for atherogenic effects and incorporation of oxyphytosterols in the lesion [14]. However, also in this case serum concentrations are low due to the low percent absorption of oxyphytosterol from the diet.…”