Kinetics of plasma Apolipoprotein E isoforms by LC-MS/MS: a pilot study
Résumé
Human apolipoprotein E (apoE) exhibits three major isoforms (apoE2, apoE3, and apoE4) corresponding to polymorphism in theAPOEgene. Total plasma apoE concentrations are closely related to these isoforms but the underlying mechanisms are unknown. We aimed to describe the kinetics of apoE individual isoforms to explore the mechanisms for variable total apoE plasma concentrations. We used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to discriminate between isoforms by identifying specific peptide sequences in subjects (3 E2/E3, 3 E3/E3 and 3 E3/E4 phenotypes) who received a primed constant infusion of2H3-leucine for 14 hours. ApoE concentrations and leucine enrichments were measured hourly in plasma. Concentrations of apoE2 were higher than apoE3, and concentrations of apoE4 were lower than apoE3. There was no difference between apoE3 and apoE4 catabolic rates and between apoE2 and apoE3 production rates, but apoE2 catabolic rates and apoE4 production rates were lower. Then, the mechanisms leading to the difference in total plasma apoE concentrations are related to contrasted kinetics of the isoforms. Production or catabolic rates are differently affected according to the specific isoforms. From these grounds, studies on the regulation of the involved biochemical pathways and the impact of pathological environments are now warranted.
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