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

Abstract Introduction High 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. Objectives This study assessed if increased α-tocopherol within HDL 2 and HDL 3 (HDL 2&3 ) influenced their antiatherogenic potential. In the first of two in vitro investigations, the oxidation potential of HDL 2&3 was assessed when α-tocopherol was added following their isolation. In the second, their oxidation potential was assessed when HDL 2&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 HDL 2&3 -associated enzymes, paraoxonase-1 (PON-1) and lecithin cholesteryl acyltransferase (LCAT). Results Conflicting results arose from the in vitro investigations, whereby increasing concentrations of α-tocopherol protected HDL 2&3 against oxidation in the post-incubated HDL 2&3 , and promoted HDL 2&3 -oxidation when they were isolated from serum pre-incubated with α-tocopherol. Following the 6-week placebo-controlled investigation, α-tocopherol increased in HDL 2&3 , while HDL 2&3 became more susceptible to oxidation, additionally the activities of HDL 2&3 -PON-1 and HDL 2 -LCAT decreased. Conclusion These results have shown for the first time that α-tocopherol induces changes to HDL 2&3 , which could contribute to the pathophysiology of cardiovascular disease.