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Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Silbernagel, G; Steiner, LK; Hollstein, T; Fauler, G; Scharnagl, H; Stojakovic, T; Schumann, F; Bölükbasi, B; März, W; Steinhagen-Thiessen, E; Laufs, U; Kassner, U.
The interrelations between PCSK9 metabolism and cholesterol synthesis and absorption.
J Lipid Res. 2019; 60(1): 161-167.
Doi: 10.1194/jlr.P088583
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Web of Science
PubMed
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- Führende Autor*innen der Med Uni Graz
- Silbernagel Günther
- Co-Autor*innen der Med Uni Graz
- Fauler Günter
- März Winfried
- Scharnagl Hubert
- Stojakovic Tatjana
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- Abstract:
- Very few studies have investigated the interrelations between proprotein convertase subtilisin/kexin type 9 (PCSK9) metabolism, cholesterol synthesis, and cholesterol absorption. We aimed to address this issue in a large clinical trial of 245 patients with hypercholesterolemia. Serum lipids, PCSK9, lathosterol (cholesterol synthesis marker), campesterol, and sitosterol (cholesterol absorption markers) were measured before and 4-8 weeks after the start of treatment with PCSK9-antibodies (alirocumab or evolocumab). The patients had mean (standard error) LDL-cholesterol and PCSK9 concentrations of 3.87 (0.10) mmol/l and 356 (17) ng/ml, respectively. Eighty-four patients received no lipid-lowering pretreatment, 26 ezetimibe, 38 statins, and 97 ezetimibe + statins. Circulating PCSK9 increased in parallel with the potency of lipid-lowering pretreatment with circulating PCSK9 being highest in the ezetimibe + statin group (P < 0.001). Treatment with PCSK9-antibodies strongly decreased LDL-cholesterol, lathosterol, campesterol, and sitosterol (all P < 0.001) but hardly affected noncholesterol sterol to cholesterol ratios. Lipid-lowering pretreatment was not associated with the effects of PCSK9-antibodies on noncholesterol sterols (all P > 0.05). Summing up, circulating PCSK9 is increased by cholesterol synthesis and absorption inhibitors. Increased PCSK9 expression may partly explain the strong reductions of LDL-cholesterol achieved with PCSK9-antibodies after such pretreatment. On the other hand, treatment with PCSK9-antibodies does not significantly change the balance between cholesterol synthesis and absorption.
- Find related publications in this database (Keywords)
- cholesterol/absorption
- cholesterol/biosynthesis
- cholesterol metabolism
- clinical trials
- low density lipoprotein
- proprotein convertase subtilisin/kexin type 9