Title
Oncostatin M reduces atherosclerosis development in APOE*3Leiden.CETP mice and is associated with increased survival probability in humans
Author
van Keulen, D.
Pouwer, M.G.
Emilsson, V.
Matic LP,
Pieterman, E.J.
Hedin, U.
Gudnason, V.
Jennings, L.L.
Holmstrøm, K.
Nielsen, B.S.
Pasterkamp, G.
Lindeman, J.H.N.
van Gool, A.J.
Sollewijn Gelpke, M.D.
Princen, H.M.G.
Tempel, D.
Publication year
2019
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.
Subject
Atherosclerosis
Oncostatin M
Biomedical Innovation
Healthy Living
Life Life
MHR - Metabolic Health Research
ELSS - Earth, Life and Social Sciences
To reference this document use:
http://resolver.tudelft.nl/uuid:2b3f0851-daca-4715-8603-50457998b9e0
DOI
https://doi.org/10.1371/journal.pone.0221477
TNO identifier
868747
Source
Plos One, 14 (14), e0221477
Document type
article