10.1371/journal.pone.0221477 Danielle van Keulen Danielle van Keulen Marianne G. Pouwer Marianne G. Pouwer Valur Emilsson Valur Emilsson Ljubica Perisic Matic Ljubica Perisic Matic Elsbet J. Pieterman Elsbet J. Pieterman Ulf Hedin Ulf Hedin Vilmundur Gudnason Vilmundur Gudnason Lori L. Jennings Lori L. Jennings Kim Holmstrøm Kim Holmstrøm Boye Schnack Nielsen Boye Schnack Nielsen Gerard Pasterkamp Gerard Pasterkamp Jan H. N. Lindeman Jan H. N. Lindeman Alain J. van Gool Alain J. van Gool Maarten D. Sollewijn Gelpke Maarten D. Sollewijn Gelpke Hans M. G. Princen Hans M. G. Princen Dennie Tempel Dennie Tempel Oncostatin M reduces atherosclerosis development in APOE*3Leiden.CETP mice and is associated with increased survival probability in humans Public Library of Science 2019 AGES LIFR Ly -6C High monocytes artery Leukemia Inhibitory Factor Receptor atherosclerosis development Oncostatin M APOE atherosclerotic lesion size plasma E-selectin levels results Gene expression analysis Chronic OSM administration OSMR serum OSM levels post incident CHD survival probability 2019-08-28 17:33:39 Dataset https://plos.figshare.com/articles/dataset/Oncostatin_M_reduces_atherosclerosis_development_in_APOE_3Leiden_CETP_mice_and_is_associated_with_increased_survival_probability_in_humans/9744122 <div><p>Objective</p><p>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.</p><p>Approach and results</p><p>Gene expression analysis on human normal arteries (n = 10) and late stage/advanced carotid atherosclerotic arteries (n = 127) and <i>in situ</i> hybridization on early human plaques (n = 9) showed that <i>OSM</i>, and its receptors, OSM receptor (<i>OSMR</i>) and Leukemia Inhibitory Factor Receptor (<i>LIFR</i>) 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-6C<sup>High</sup> 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).</p><p>Conclusions</p><p>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.</p></div>