α-Tocopherol induces proatherogenic changes to HDL2 & HDL3: An in vitro and ex vivo investigation

IntroductionHigh density lipoproteins (HDL) have considerable potential for improving cardiovascular health. Additionally, epidemiological studies have identified an inverse relationship between α-tocopherol intake and cardiovascular disease, which has not been translated in randomised controlled trials.ObjectivesThis study assessed if increased α-tocopherol within HDL2 and HDL3 (HDL2&3) influenced their antiatherogenic potential. In the first of two in vitro investigations, the oxidation potential of HDL2&3 was assessed when α-tocopherol was added following their isolation. In the second, their oxidation potential was assessed when HDL2&3 were isolated from serum pre-incubated with α-tocopherol. Additionally, a 6-week placebo-controlled intervention with α-tocopherol assessed if α-tocopherol influenced the oxidation potential and activities of HDL2&3-associated enzymes, paraoxonase-1 (PON-1) and lecithin cholesteryl acyltransferase (LCAT).ResultsConflicting results arose from the in vitro investigations, whereby increasing concentrations of α-tocopherol protected HDL2&3 against oxidation in the post-incubated HDL2&3, and promoted HDL2&3-oxidation when they were isolated from serum pre-incubated with α-tocopherol. Following the 6-week placebo-controlled investigation, α-tocopherol increased in HDL2&3, while HDL2&3 became more susceptible to oxidation, additionally the activities of HDL2&3-PON-1 and HDL2-LCAT decreased.ConclusionThese results have shown for the first time that α-tocopherol induces changes to HDL2&3, which could contribute to the pathophysiology of cardiovascular disease.

► Assessed if increasing α-tocopherol within HDL2&3 influenced their atherogenicity. ► In vitro tocopherol protected HDL2&3 from oxidation when added following isolation. ► In vitro tocopherol promoted HDL2&3 oxidation when added prior to their isolation. ► Ex vivo tocopherol promoted HDL2&3 oxidation and altered PON-1 & LCAT activities. ► These results may explain why tocopherol has been ineffective in preventing CVD.