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Oncostatin M reduces atherosclerosis development in APOE*3Leiden.CETP mice and is associated with increased survival probability in humans

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posted on 2019-08-28, 17:33 authored by Danielle van Keulen, Marianne G. Pouwer, Valur Emilsson, Ljubica Perisic Matic, Elsbet J. Pieterman, Ulf Hedin, Vilmundur Gudnason, Lori L. Jennings, Kim Holmstrøm, Boye Schnack Nielsen, Gerard Pasterkamp, Jan H. N. Lindeman, Alain J. van Gool, Maarten D. Sollewijn Gelpke, Hans M. G. Princen, Dennie Tempel

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.

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