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

van Keulen, Danielle and Pouwer, Marianne G. and Emilsson, Valur and Aldi, Silvia and Perisic Matic, Ljubica and Hedin, Ulf and Gudnason, Vilmundur and Jennings, Lori and Holstrom, Kim and Schnack Nielson, Boye and Pasterkamp, Gerard and Lindeman, Jan H.N. and van Gool, Alain J. and Sollewijn Gelpke, Maarten D. and Princen, Hans M.G. and Tempel, Dennie (2019) Oncostatin M reduces atherosclerosis development in APOE3Leiden.CETP mice and is associated with increased survival probability in humans. PLoS ONE, 14 (8). pp. 1-22. ISSN 19326203

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. 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). 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.

Item Type: Article
Date Deposited: 15 Oct 2019 00:45
Last Modified: 15 Oct 2019 00:45
URI: https://oak.novartis.com/id/eprint/38307

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