Anti-PCSK9 antibodies inhibit pro-atherogenic mechanisms in APOE*3Leiden.CETP mice

Scientific Reports
Susanne SchusterUlrich Laufs

Abstract

LDL-cholesterol (LDL-C) is a causal pathogenic factor in atherosclerosis. Monoclonal anti-proprotein convertase subtilisin/kexin type 9 (PCSK9) neutralizing antibodies are novel potent LDL-lowering drugs which reduce cardiovascular events. To characterize their effect on atherogenesis, APOE*3Leiden.CETP mice were fed a high cholesterol/high fat diet (WTD) or normal chow (NC) for 18 weeks. Mice on WTD were injected with the human anti-PCSK9 antibody mAb1 (PL-45134, 10 mg*kg-1 s.c.) or 0.9% saline every 10 days. PCSK9 inhibition decreased total cholesterol in serum of APOE*3Leiden.CETP mice and prevented the development of atherosclerosis. The plaque area in the aortic root was reduced by half and macrophage infiltration determined by Ly6c and Mac-3 staining was ameliorated. PCSK9 inhibition decreased markers of inflammation in mononuclear cells (Il-6, Tnfa mRNA), and in serum (CXCL-1,-10,-13; complement factor C5a) compared to control WTD fed animals. The number of circulating Sca-1/VEGF-R2 positive endothelial progenitor cells of the peripheral blood and spleen-derived diLDL/lectin double positive circulating angiogenic cells was increased. To conclude, the PCSK9-mediated anti-atherosclerotic effect involves the upregulation of...Continue Reading

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Citations

Aug 28, 2020·The New England Journal of Medicine·Rocco Vergallo, Filippo Crea
Feb 12, 2021·Journal, Genetic Engineering & Biotechnology·Anuran GhoshPraphulla Chandra Shukla
Dec 12, 2020·Frontiers in Physiology·Julius L KatzmannUlrich Laufs
Jun 24, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Yihan ZhaoDazhuo Shi
Apr 10, 2021·Frontiers in Cardiovascular Medicine·Aureli LuqueroMaria Borrell-Pages
Apr 25, 2021·Catheterization and Cardiovascular Interventions : Official Journal of the Society for Cardiac Angiography & Interventions·Tiziana Claudia AranzullaAndrea Gaggiano

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Methods Mentioned

BETA
PCR
FACS
density gradient centrifugation
flow cytometry
Profiler

Software Mentioned

ImageJ
NIS
Pannoramic Viewer
Graph Pad Prism
Graph Pad
Cell Quest

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