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Oncostatin M reduces atherosclerosis development in APOE*3Leiden.CETP mice and is associated with increased survival probability in humans.
- Source :
-
PloS one [PLoS One] 2019 Aug 28; Vol. 14 (8), pp. e0221477. Date of Electronic Publication: 2019 Aug 28 (Print Publication: 2019). - Publication Year :
- 2019
-
Abstract
- Objective: Previous studies indicate a role for Oncostatin M (OSM) in atherosclerosis and other chronic inflammatory diseases for which inhibitory antibodies are in development. However, to date no intervention studies with OSM have been performed, and its relation to coronary heart disease (CHD) has not been studied.<br />Approach and Results: Gene expression analysis on human normal arteries (n = 10) and late stage/advanced carotid atherosclerotic arteries (n = 127) and in situ hybridization on early human plaques (n = 9) showed that OSM, and its receptors, OSM receptor (OSMR) and Leukemia Inhibitory Factor Receptor (LIFR) are expressed in normal arteries and atherosclerotic plaques. Chronic OSM administration in APOE*3Leiden.CETP mice (n = 15/group) increased plasma E-selectin levels and monocyte adhesion to the activated endothelium independently of cholesterol but reduced the amount of inflammatory Ly-6CHigh monocytes and atherosclerotic lesion size and severity. Using aptamer-based proteomics profiling assays high circulating OSM levels were shown to correlate with post incident CHD survival probability in the AGES-Reykjavik study (n = 5457).<br />Conclusions: Chronic OSM administration in APOE*3Leiden.CETP mice reduced atherosclerosis development. In line, higher serum OSM levels were correlated with improved post incident CHD survival probability in patients, suggesting a protective cardiovascular effect.<br />Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: Danielle van Keulen and Dennie Tempel are employed by Quorics B.V., Maarten D Sollewijn Gelpke by Molecular Profiling Consulting, Lori L Jennings by Novartis and Kim Holmstrøm and Boye Schnack Nielsen PhD by Bioneer A/S. There are no patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials,as detailed online in the guide for authors.
- Subjects :
- Animals
Atherosclerosis blood
Atherosclerosis genetics
Biomarkers metabolism
Coronary Disease blood
Coronary Disease genetics
Coronary Disease mortality
Endothelial Cells metabolism
Endothelial Cells pathology
Female
Humans
Inflammation pathology
Interleukin-6 metabolism
Leukemia Inhibitory Factor Receptor alpha Subunit genetics
Leukemia Inhibitory Factor Receptor alpha Subunit metabolism
Mice, Transgenic
Monocytes pathology
Oncostatin M blood
Oncostatin M genetics
Oncostatin M Receptor beta Subunit genetics
Oncostatin M Receptor beta Subunit metabolism
Phenotype
Plaque, Atherosclerotic genetics
Plaque, Atherosclerotic pathology
Probability
RNA, Messenger genetics
RNA, Messenger metabolism
Survival Analysis
Vascular Cell Adhesion Molecule-1 metabolism
Apolipoproteins E metabolism
Atherosclerosis pathology
Cholesterol Ester Transfer Proteins metabolism
Oncostatin M metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 14
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 31461490
- Full Text :
- https://doi.org/10.1371/journal.pone.0221477