PCSK9 inhibition alters the lipidome of plasma and lipoprotein fractions

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http://hdl.handle.net/10138/300883

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Hilvo , M , Simolin , H , Metso , J , Ruuth , M , Öörni , K , Jauhiainen , M , Laaksonen , R & Baruch , A 2018 , ' PCSK9 inhibition alters the lipidome of plasma and lipoprotein fractions ' , Atherosclerosis , vol. 269 , pp. 159-165 . https://doi.org/10.1016/j.atherosclerosis.2018.01.004

Title: PCSK9 inhibition alters the lipidome of plasma and lipoprotein fractions
Author: Hilvo, Mika; Simolin, Helena; Metso, Jari; Ruuth, Maija; Öörni, Katariina; Jauhiainen, Matti; Laaksonen, Reijo; Baruch, Amos
Contributor: University of Helsinki, Medicum
Date: 2018-02
Language: eng
Number of pages: 7
Belongs to series: Atherosclerosis
ISSN: 0021-9150
URI: http://hdl.handle.net/10138/300883
Abstract: Background and aims: While inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) is known to result in dramatic lowering of LDL-cholesterol (LDL-C), it is poorly understood how it affects other lipid species and their metabolism. The aim of this study was to characterize the alterations in the lipidome of plasma and lipoprotein particles after administration of PCSK9 inhibiting antibody to patients with established coronary heart disease. Methods: Plasma samples were obtained from patients undergoing a randomized placebo-controlled phase II trial (EQUATOR) for the safe and effective use of RG7652, a fully human monoclonal antibody inhibiting PCSK9 function. Lipoprotein fractions were isolated by sequential density ultracentrifugation, and both plasma and major lipoprotein classes (VLDL-IDL, LDL, HDL) were subjected to mass spectrometric lipidomic profiling. Results: PCSK9 inhibition significantly decreased plasma levels of several lipid classes, including sphingolipids (dihydroceramides, glucosylceramides, sphingomyelins, ceramides), cholesteryl esters and free cholesterol. Previously established ceramide ratios predicting cardiovascular mortality, or inflammation related eicosanoid lipids, were not altered. RG7652 treatment also affected the overall and relative distribution of lipids in lipoprotein classes. An overall decrease of total lipid species was observed in LDL and VLDL thorn IDL particles, while HDL-associated phospholipids increased. Following the treatment, LDL displayed reduced lipid cargo, whereas relative lipid proportions of the VLDL thorn IDL particles were mostly unchanged, and there were relatively more lipids carried in the HDL particles. Conclusions: Administration of PCSK9 antibody significantly alters the lipid composition of plasma and lipoprotein particles. These changes further shed light on the link between anti-PCSK9 therapies and cardiovascular risk. (C) 2018 Elsevier B.V. All rights reserved.
Subject: PCSK9
Lipidomics
Lipoproteins
Atherosclerosis
Sphingolipids
Drug therapy
CORONARY-ARTERY-DISEASE
HEART-DISEASE
LDL-C
HYPERCHOLESTEROLEMIA
INFLAMMATION
DEFICIENCY
RISK
3111 Biomedicine
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