Anti-PCSK9 antibodies inhibit pro-atherogenic mechanisms in APOE*3Leiden.CETP mice
| Autor: | Christian Werner, Susanne Schuster, Sandra Rubil, Matthias Endres, Karsten Winter, Ulrich Laufs, J.-N Boeckel, Hans M.G. Princen |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Apolipoprotein E lcsh:Medicine Biomedical Innovation Cardiovascular metabolism [Endothelial Progenitor Cells] metabolism [Apolipoproteins E] Mice 0302 clinical medicine Life Lectins metabolism [Atherosclerosis] lcsh:Science Endothelial Progenitor Cells Hypolipidemic Agents metabolism [Inflammation] drug effects [Macrophages] Multidisciplinary biology Chemistry Antibodies Monoclonal Plaque Atherosclerotic Up-Regulation drug effects [Up-Regulation] Cholesterol metabolism [Cholesterol LDL] physiology [Antibodies Monoclonal] drug effects [Endothelial Progenitor Cells] metabolism [Lectins] Tumor necrosis factor alpha lipids (amino acids peptides and proteins) Antibody medicine.symptom Proprotein Convertase 9 MHR - Metabolic Health Research Healthy Living medicine.medical_specialty Cardiology Inflammation Complement factor I Peripheral blood mononuclear cell Article Antibodies drug therapy [Atherosclerosis] 03 medical and health sciences Apolipoproteins E Internal medicine metabolism [Proprotein Convertase 9] medicine Animals Humans pharmacology [Hypolipidemic Agents] Progenitor cell drug therapy [Plaque Atherosclerotic] PCSK9 Macrophages lcsh:R Cholesterol LDL Atherosclerosis metabolism [Cholesterol] Cardiovascular biology 030104 developmental biology Endocrinology biology.protein metabolism [Macrophages] lcsh:Q ELSS - Earth Life and Social Sciences ddc:600 metabolism [Plaque Atherosclerotic] 030217 neurology & neurosurgery |
| Zdroj: | Scientific reports 9(1), 11079 (2019). doi:10.1038/s41598-019-47242-0 Scientific Reports, 1, 9 Scientific Reports, Vol 9, Iss 1, Pp 1-8 (2019) Scientific Reports |
| Popis: | 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 pro-regeneratory endothelial progenitor cells, a reduction of inflammation and change of plaque composition. |
| Databáze: | OpenAIRE |
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