Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Jänis, MT; Tarasov, K; Ta, HX; Suoniemi, M; Ekroos, K; Hurme, R; Lehtimäki, T; Päivä, H; Kleber, ME; März, W; Prat, A; Seidah, NG; Laaksonen, R.
Beyond LDL-C lowering: distinct molecular sphingolipids are good indicators of proprotein convertase subtilisin/kexin type 9 (PCSK9) deficiency.
Atherosclerosis. 2013; 228(2):380-385
Doi: 10.1016/j.atherosclerosis.2013.03.029
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- Co-Autor*innen der Med Uni Graz
- März Winfried
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- Abstract:
- Objectives: Inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) has been proposed to be a potential new therapeutic target for treatment of hypercholesterolaemia. However, little is known about the effects of PCSK9 inhibition on the lipidome. Methods: We performed molecular lipidomic analyses of plasma samples obtained from PCSK9-deficient mice, and serum of human carriers of a loss-of-function variant in the PCSK9 gene (R46L). Results: In both mouse and man, PCSK9 deficiency caused a decrease in several cholesteryl esters (CE) and short fatty acid chain containing sphingolipid species such as CE 16: 0, glucosyl/galactosylceramide (Glc/GalCer) d18:1/16:0, and lactosylceramide (LacCer) d18:1/16:0. In mice, the changes in lipid concentrations were most prominent when animals were given regular chow diet. In man, a number of molecular lipid species was shown to decrease significantly even when LDL-cholesterol was non-significantly reduced by 10% only. Western diet attenuated the lipid lowering potency of PCSK9 deficiency in mice. Conclusions: Plasma molecular lipid species may be utilized for characterizing novel compounds inhibiting PCSK9 and as sensitive efficacy markers of the PCSK9 inhibition. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Biological Markers - blood
- Cholesterol Esters - blood
- Cholesterol, LDL - blood
- Genotype -
- Humans -
- Male -
- Mice -
- Mice, Knockout -
- Mutation -
- Phenotype -
- Proprotein Convertases - deficiency
- Prospective Studies -
- Serine Endopeptidases - deficiency
- Sphingolipids - blood
- Find related publications in this database (Keywords)
- PCSK9
- Biomarker
- Lipidomics