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Oncostatin M receptor β deficiency attenuates atherogenesis by inhibiting JAK2/STAT3 signaling in macrophages

Xin Zhang1,2,3, Jing Li1, Juan-Juan Qin1,2,3

  • 1Department of Cardiology, Renmin Hospital, Wuhan University, Wuhan, China.

Journal of Lipid Research
|March 5, 2017
PubMed

Insights

Oncostatin M receptor beta (OSMR-β) deficiency in macrophages ameliorates atherosclerosis. This protection involves enhanced plaque stability and reduced inflammation, potentially via inhibiting the JAK2/STAT3 pathway.

Area of Science:

  • Cardiovascular Biology
  • Immunology
  • Molecular Medicine

Background:

  • Oncostatin M (OSM) is a cytokine implicated in chronic inflammatory and cardiovascular diseases.
  • OSM receptor beta (OSMR-β) mediates OSM's effects, and its role in atherosclerosis is under investigation.
  • Previous studies suggest OSM destabilizes atherosclerotic plaques.

Purpose of the Study:

  • To investigate the impact of OSMR-β deficiency on atherosclerosis development and plaque stability.
  • To elucidate the underlying molecular mechanisms, particularly the involvement of the JAK2/STAT3 signaling pathway in macrophages.

Main Methods:

  • Generated and studied male OSMR-β knockout (OSMR-β-/-) and Apolipoprotein E knockout (ApoE-/-) mice fed a high-fat diet.
  • Analyzed atherosclerotic lesions in the aorta and aortic root for burden, composition, and stability markers.
  • Utilized bone marrow transplantation experiments and in vitro studies with oxidized low-density lipoprotein (Ox-LDL) stimulation.

Main Results:

  • OSMR-β expression was significantly upregulated in human and mouse atherosclerotic lesions, primarily in macrophages.
  • OSMR-β deficiency markedly reduced atherosclerotic burden and enhanced plaque stability by increasing collagen and smooth muscle cell content.
  • OSMR-β deficiency decreased macrophage infiltration and lipid accumulation in plaques and was associated with reduced JAK2/STAT3 activation.

Conclusions:

  • OSMR-β deficiency in macrophages confers significant protection against high-fat diet-induced atherosclerosis and plaque vulnerability.
  • The protective effects are partly mediated by the inhibition of the JAK2/STAT3 signaling pathway in macrophages.
  • Targeting OSMR-β in macrophages represents a potential therapeutic strategy for cardiovascular diseases like atherosclerosis.
Keywords:
Janus kinase 2/signal transducer and activator of transcription 3atherosclerosisinflammation

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