Activation of Lipid Mediator Formation Due to Lipoprotein Apheresis

Nutrients. 2019 Feb 9;11(2):363. doi: 10.3390/nu11020363.

Abstract

Lipoprotein apheresis reliably reduces low-density lipoprotein (LDL) cholesterol in patients with atherosclerotic disease and therapy-refractory hypercholesterolemia or elevated lipoprotein (a) (Lp(a)). Besides lowering lipoproteins and triglycerides, apheresis also decreases levels of essential omega-6 and omega-3 polyunsaturated fatty acids (n-6 and n-3 PUFAs) in blood plasma. In contrast, heparin-induced extracorporeal low-density lipoprotein precipitation (HELP) lipid apheresis might increase the formation of potentially pro-inflammatory and pro-thrombotic lipid mediators derived from n-6 and n-3 PUFAs. The study presented here analyzed lipid mediator profiles in the plasma of patients with hyperlipidemia treated by one of three different apheresis methods, either HELP, direct absorption (DA), or membrane filtration (MDF), in a direct pre- and post-apheresis comparison. Using gas chromatography and liquid chromatography tandem mass spectrometry (LC-MS/MS) we were able to analyze fatty acid composition and the formation of lipid mediators called oxylipins. Our data illustrate-particularly in HELP-treated patients-significant decreases of essential omega-6 and omega-3 polyunsaturated fatty acids in blood plasma but significant increases of PUFA-derived lipoxygenase-, as well as cyclooxygenase- and cytochrome P450-derived lipid mediators. Given that n-3 PUFAs in particular are presumed to be cardioprotective and n-3 PUFA-derived lipid mediators might limit inflammatory reactions, these data indicate that n-3 PUFA supplementation in the context of lipid apheresis treatment might have additional benefits through apheresis-triggered protective n-3 PUFA-derived lipid mediators.

Keywords: LC-MS/MS; docosahexaenoic acid; gas chromatography; hyperlipoproteinaemia; lipid apheresis; lipid mediators; lipidomics; n-3 PUFA; n-6 PUFA.; omega-3 polyunsaturated fatty acids, eicosapentaenoic acid; oxylipins.

MeSH terms

  • Blood Component Removal / adverse effects
  • Blood Component Removal / methods*
  • Chromatography, Liquid
  • Fatty Acids, Omega-3 / blood
  • Fatty Acids, Omega-3 / isolation & purification*
  • Fatty Acids, Omega-6 / blood
  • Fatty Acids, Omega-6 / isolation & purification*
  • Female
  • Gas Chromatography-Mass Spectrometry
  • Heparin
  • Humans
  • Lipoproteins, LDL / blood
  • Lipoproteins, LDL / isolation & purification*
  • Male
  • Middle Aged
  • Tandem Mass Spectrometry

Substances

  • Fatty Acids, Omega-3
  • Fatty Acids, Omega-6
  • Lipoproteins, LDL
  • Heparin