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

被引：8

作者：

van Keulen, Danielle ^{[1
,2
,3
,4
]}

Pouwer, Marianne G. ^{[4
,5
]}

Emilsson, Valur ^{[6
,7
]}

Matic, Ljubica Perisic ^{[8
]}

Pieterman, Elsbet J. ^{[4
]}

Hedin, Ulf ^{[8
]}

Gudnason, Vilmundur ^{[6
,9
]}

Jennings, Lori L. ^{[10
]}

Holmstrom, Kim ^{[11
]}

Nielsen, Boye Schnack ^{[11
]}

Pasterkamp, Gerard ^{[2
]}

Lindeman, Jan H. N. ^{[12
]}

van Gool, Alain J. ^{[13
]}

Gelpke, Maarten D. Sollewijn ^{[14
]}

Princen, Hans M. G. ^{[4
]}

Tempel, Dennie ^{[1
,2
,3
,15
]}

机构：

[1] Univ Med Ctr Utrecht, Lab Expt Cardiol, Utrecht, Netherlands

[2] Univ Med Ctr Utrecht, Lab Clin Chem & Haematol, Utrecht, Netherlands

[3] Quorics BV, Rotterdam, Netherlands

[4] Gaubius Lab, TNO Metab Hlth Res, Leiden, Netherlands

[5] Leiden Univ, Dept Cardiol, Med Ctr, Leiden, Netherlands

[6] Iceland Heart Assoc, Kopavogur, Iceland

[7] Univ Iceland, Fac Pharmaceut Sci, Reykjavik, Iceland

[8] Karolinska Inst, Dept Mol Med & Surg, Solna, Sweden

[9] Univ Iceland, Fac Med, Reykjavik, Iceland

[10] Novartis Inst Biomed Res, Cambridge, MA USA

[11] Bioneer AS, Horsholm, Denmark

[12] Leiden Univ, Dept Vasc Surg, Med Ctr, Leiden, Netherlands

[13] TNO Microbiol & Syst Biol, Zeist, Netherlands

[14] Mol Profiling Consulting, London, England

[15] SkylineDx BV, Rotterdam, Netherlands

来源：

PLOS ONE | 2019年 / 14卷 / 08期

基金：

瑞典研究理事会;

关键词：

SMOOTH-MUSCLE-CELLS; NECROSIS-FACTOR-ALPHA; INHIBITS ATHEROSCLEROSIS; NATURAL-HISTORY; EXPRESSION; INFLAMMATION; CYTOKINES; CHOLESTEROL; MACROPHAGES; NEUTROPHILS;

D O I：

10.1371/journal.pone.0221477

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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-6C High 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.

引用

页数：22