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>