HDL enhances oxidation of LDL in vitro in both men and women

Abstract

BackgroundOxidative modification of low-density lipoprotein (LDL) is a key event in the oxidation hypothesis of atherogenesis. Some in vitro experiments have previously suggested that high-density lipoprotein (HDL) co-incubated with LDL prevents Cu2+-induced oxidation of LDL, while some other studies have observed an opposite effect. To comprehensively clarify the role of HDL in this context, we isolated LDL, HDL2 and HDL3 from sera of 61 free-living individuals (33 women and 28 men).ResultsWhen the isolated LDL was subjected to Cu2+-induced oxidation, both HDL2 and HDL3 particles increased the rate of appearance and the final concentration of conjugated dienes similarly in both genders. Oxidation rate was positively associated with polyunsaturated fatty acid content of the lipoproteins in that it was positively related to the content of linoleate and negatively related to oleate. More saturated fats thus protected the lipoproteins from damage.ConclusionWe conclude that in vitro HDL does not protect LDL from oxidation, but is in fact oxidized fastest of all lipoproteins due to its fatty acid composition, which is oxidation promoting.

Delta-6-desaturase gene polymorphism is associated with lipoprotein oxidation in vitro

“…This procedure has been shown to preserve LDL from oxidation for at least two months and the oxidation curve does not differ from that of a fresh sample [17]. Lipids were analysed as described [6]. All samples were kept frozen at −70°C until analyzed.…”

“…Lipoproteins were fractionated by isopycnic density gradient ultracentrifugation using a Beckman SW40 Ti rotor in a Beckman L60 centrifuge (36000 rpm, 40 hours, 10°C) as previously described [6]. The fatty acid compositions were analyzed by capillary gas–liquid chromatography [6,7].…”

“…The fatty acid compositions were analyzed by capillary gas–liquid chromatography [6,7]. From fatty acid compositions, the peroxidizability index was calculated: (PI) = [(Σ mol% monoenoic FAs × 0.025) + (Σ mol% dienoic FAs × 1) + (Σ mol% trienoic FAs × 2) + (Σ mol% tetraenoic FAs × 4) + (Σ mol% pentaenoic FAs × 6) + (Σ mol% hexaenoic FAs × 8)] [14].…”

“…The susceptibility of mixtures of LDL and HDL 2 or HDL 3 subtractions to in vitro copper-catalyzed oxidation was assessed by continuously monitoring the production of conjugated dienes at 234 nm, as previously described [6,18]. Oxidation was started by adding 10 μl of CuSO4 to a final concentration of 1.65 μM Cu 2+ .…”

“…PUFA play an important role in atherosclerosis through regulation of cholesterol transport by lipoproteins, and oxidative modification of low-density lipoprotein (LDL) is a key event in the oxidation hypothesis of atherogenesis [5]. We have previously shown that HDL does not protect LDL from oxidation in vitro , but is in fact oxidized fastest of all lipoproteins due to its rich polyunsaturated fatty acid (PUFA) composition, which is oxidation promoting [6]. In the present study, we tested the effect of FADS2 rs 3834458 on lipoprotein oxidation in vitro, in plasma derived from healthy subjects.…”