Oncostatin M reduces atherosclerosis development in APOE3Leiden.CETP mice and is associated with increased survival probability in humans

• Published in: PloS one Vol. 14; no. 8; p. e0221477
• Main Authors: Keulen, Danielle van, Pouwer, Marianne G, Emilsson, Valur, Matic, Ljubica Perisic, Pieterman, Elsbet J, Hedin, Ulf, Gudnason, Vilmundur, Jennings, Lori L, Holmstrøm, Kim, Nielsen, Boye Schnack, Pasterkamp, Gerard, Lindeman, Jan H N, van Gool, Alain J, Sollewijn Gelpke, Maarten D, Princen, Hans M G, Tempel, Dennie
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 28.08.2019; Public Library of Science (PLoS)
• Subjects: Angiogenesis; Animals; Antibodies; Apolipoprotein E; Apolipoproteins; Apolipoproteins E - metabolism; Aptamers; Arteries; Arteriosclerosis; Atherosclerosis; Atherosclerosis - blood; Atherosclerosis - genetics; Atherosclerosis - pathology; Biology and Life Sciences; Biomarkers - metabolism; Cardiology; Cardiovascular disease; Cardiovascular diseases; Cholesterol; Cholesterol Ester Transfer Proteins - metabolism; Coronary artery disease; Coronary Disease - blood; Coronary Disease - genetics; Coronary Disease - mortality; Coronary heart disease; Coronary vessels; Criminal investigation; Cytokines; Development and progression; E-selectin; Endothelial Cells - metabolism; Endothelial Cells - pathology; Endothelium; Female; Gene expression; Genetic aspects; Heart attacks; Heart diseases; Hematology; Humans; Hybridization; Inflammation - pathology; Inflammatory diseases; Interleukin-6 - metabolism; Laboratories; Leukemia; Leukemia inhibitory factor; Leukemia Inhibitory Factor Receptor alpha Subunit - genetics; Leukemia Inhibitory Factor Receptor alpha Subunit - metabolism; Levels; Lipoproteins; Ly-6 antigen; Medical research; Medicin och hälsovetenskap; Medicine and Health Sciences; Metabolism; Mice; Mice, Transgenic; Monocytes; Monocytes - pathology; Neutrophils; Oncostatin M; Oncostatin M - blood; Oncostatin M - genetics; Oncostatin M - metabolism; Oncostatin M Receptor beta Subunit - genetics; Oncostatin M Receptor beta Subunit - metabolism; Phenotype; Physiological aspects; Plaque, Atherosclerotic - genetics; Plaque, Atherosclerotic - pathology; Plaques; Probability; Proteomics; Public access; Receptors; Rheumatoid arthritis; RNA, Messenger - genetics; RNA, Messenger - metabolism; Studies; Surgery; Survival; Survival Analysis; Vascular Cell Adhesion Molecule-1 - metabolism; Veins & arteries; Netherlands; Denmark; Sweden; United States > US; Massachusetts; Iceland
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0221477

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. 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). 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.