Activation of Lipid Mediator Formation Due to Lipoprotein Apheresis.

Karsten-H Weylandt,Christoph Schmöcker,Ursula Kassner,Elisabeth Steinhagen-Thiessen,Nils Helge Schebb,Ina Willenberg,Annika I Ostermann,Laura Kutzner,Stefanie Kiesler

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.

Highlights

Atherosclerosis and cardiovascular events are major causes of morbidity and mortality in patients with severe hypercholesterolemia
We showed significantly reduced polyunsaturated fatty acids (PUFAs) concentrations in plasma due to apheresis using either heparin-induced extracorporeal low-density lipoprotein precipitation (HELP, Futura® ) or low-density lipoprotein hemoperfusion and direct absorption of lipoproteins, DALI® (DA)
Lipoprotein apheresis reduced total cholesterol and low-density lipoprotein (LDL)-C by 50% and 63%, respectively, in the pre/post analysis. These results were accompanied by a mean decrease of 15.9% for high-density lipoprotein cholesterol (HDL-C) and a 51%

Summary

Introduction

Atherosclerosis and cardiovascular events are major causes of morbidity and mortality in patients with severe hypercholesterolemia. Lipoprotein (a) (Lp(a)) is an established independent cardiovascular risk factor [4]. For those patients who continue to develop clinically significant cardiovascular disease in spite of lipid-lowering medications, lipoprotein apheresis is an established therapeutic method to reduce low-density lipoprotein cholesterol (LDL-C) levels and Lp(a). Long-term lipoprotein apheresis treatment has been proven to reduce major cardiovascular events by more than 80% [5]. Apheresis decreases oxidized LDL particles and fibrinogen levels [6,7,8,9]. Lipoprotein apheresis has been shown to change plasma cytokine profiles and reduce inflammatory markers in patients with hypercholesterolemia and coronary heart disease [12]

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