Dietary oxysterols are incorporated in plasma triglyceriderich lipoproteins, increase their susceptibility to oxidation and increase aortic cholesterol concentration of rabbits

Abstract

Early fatty streaks and advanced lesions are characterized by the deposition of cholesterol and cholesterol oxidation products (oxysterols). Oxysterols have been shown to be cytotoxic and pro-atherogenic compared to cholesterol and are found in cholesterol-rich processed foods. The consumption of dietary oxysterols may be significant in the onset and development of vascular disease. In order to study the short term effects of low levels of ingested dietary oxysterols on lipoprotein and aortic cholesterol and oxysterol levels, rabbits were fed either standard chow, chow supplemented with 1.0% oxidized cholesterol (containing 6% oxysterols), or 1.0% purified cholesterol (control). To determine the distribution and uptake of oxysterols after a 2-week dietar y period, triglyceride-rich plasma lipoproteins, low density lipoproteins and aorta were analyzed by GC-MS. The concentration of 7 ␤ -hydroxycholesterol was similar in all groups but the oxidized cholesterol-fed animals showed five times the concentration of 5 ␣ ,6 ␣ -epoxycholesterol and double the level of 7-ketocholesterol in triglyceride-rich lipoproteins compared to the purified cholesterol-fed animals. The presence of 7-ketocholesterol in LDL was exclusive to animals fed the oxidized cholesterol diet. In addition, oxidation of triglyceride-rich lipoproteins was significantly greater in rabbits fed oxidized cholesterol compared to the pure cholesterol-fed animals. The oxidized cholesterol-fed animals also had a 64% increase in total aortic cholesterol, despite lower plasma cholesterol levels compared to the pure cholesterol control animals.Taken together these results suggest that dietary oxysterols may substantially increase the atherogenicity of lipoproteins.-Vine, D.

Impact of cholesterol-pathways on breast cancer development, a metabolic landscape

“…For instance, oxysterols are oxidized molecules derivatives of cholesterol, associated with pro-atherogenic properties. Oxysterol formation is related to LDL-oxidation (oxLDL) due to the inflammatory cellular responses in tunica intima [83], also factors such as diet could favor the increase in plasmatic concentrations, which in turn are incorporated in plasmatic triglyceride-rich lipoproteins [84]. Notwithstanding, HDL could remove oxidized lipids from the surface of oxLDL, including oxysterols such as 7-ketocholesterol and 7β-hydroxycholesterol [85].…”

Can Meat and Meat-Products Induce Oxidative Stress?

“…The presence of oxysterols in the body can be of endogenous origin (mainly derived from non-enzymatic processes) or exogenous, from the diet. Although oxysterol absorption rate is lower than that of cholesterol, there is a direct correlation between the amount of oxidized lipids ingested and plasma oxysterols levels [82,83]. These compounds are absorbed in the upper digestive tract and are transported by chylomicrons and other lipoproteins, being able to deposit them in peripheral tissues and increase oxidative stress.…”

HDL, ABC Transporters, and Cholesterol Efflux: Implications for the Treatment of Atherosclerosis

“…ABCG1 has a specific role in promoting cellular efflux of sterols modified at the 7 position such as 7-ketocholesterol (7-KC; Terasaka et al, 2007). 7-KC is a spontaneously formed cholesterol oxidation product that is present in processed foods and high-cholesterol diets and is the most abundant oxysterol in oxidized LDL and in human atherosclerotic plaques (Brown et al, 1996;Brown and Jessup, 1999;Vine et al, 1998) Review chylomicrons, rapidly cleared from the circulation in remnants, and converted into bile salts in the liver. However, 7-KC is apparently cytotoxic at some concentrations found in vivo, inducing apoptosis and necrosis of endothelial cells and macrophages.…”