Pycnogenol Reduces Toll-Like Receptor 4 Signaling Pathway-Mediated Atherosclerosis Formation in Apolipoprotein E-Deficient Mice

Here, we investigated the effect of chronic mild stress (CMS) on the development of atherosclerosis as well as the expression of Toll-like receptors (TLRs) signaling pathway in adolescent apolipoprotein E knockout (apoE-/-) mice. Mice were subjected to daily CMS for 0, 4, and 12 weeks, respectively. To identify the expression of Toll-like receptor 4 signaling pathway in adolescent apolipoprotein E knockout mice subjected to CMS, we compared gene expression in aortas of stressed and unstressed mice using TLRs signaling pathway real-time PCR microarrays consisting of 87 genes. We found that atherosclerosis lesions both in aortic tress and sinuses of CMS mice were significantly increased linearly in response to duration of CMS exposure. Among 87 genes analyzed, 15 genes were upregulated in stressed mice, especially TLR4, myeloid differentiation factor 88 (MyD88), and IL-1β, and 28 genes were downregulated compared with nonstressed mice. CMS mice demonstrated markedly increased aortic atherosclerosis that were associated with significant increases in levels of expression of TLR4, MyD88, nuclear factorκB (NF-κB), MCP-1, IL-1β, TNF-α, and sICAM-1. Taken together, our results suggest an important role for TLR4 signaling pathway in atherosclerosis in a CMS mouse model.

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Progress in Biochemistry and Biophysics》 2013-09Add to Favorite Get Latest Update Glycoprotein Ⅱb/Ⅲa mAb Decreases Atherosclerosis by Inhibiting High-Mobility Group Box-1/Toll-like Receptor 4 Signaling in Apolipoprotein-E-deficient Mice

ACTA AGRONOMICA SINICA ◽

10.3724/sp.j.1206.2012.00602 ◽

2013 ◽

Vol 40 (9) ◽

pp. 834

Author(s):

Hong-Feng GU ◽

Jian-Hong JIANG ◽

Duan-Fang LIAO ◽

Qiao-Zhen TONG ◽

Yong-Zong YANG

Keyword(s):

Apolipoprotein E ◽

High Mobility ◽

High Mobility Group ◽

Toll Like Receptor ◽

Toll Like Receptor 4 ◽

Deficient Mice

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Faculty Opinions recommendation of TRAM is specifically involved in the Toll-like receptor 4-mediated MyD88-independent signaling pathway.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1016387.200666 ◽

2003 ◽

Author(s):

David Underhill

Keyword(s):

Signaling Pathway ◽

Toll Like Receptor ◽

Toll Like Receptor 4

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Toll-like Receptor 4 Signaling in Ventilator-induced Diaphragm Atrophy

Anesthesiology ◽

10.1097/aln.0b013e3182608cc0 ◽

2012 ◽

Vol 117 (2) ◽

pp. 329-338 ◽

Cited By ~ 34

Author(s):

Willem-Jan M. Schellekens ◽

Hieronymus W. H. van Hees ◽

Michiel Vaneker ◽

Marianne Linkels ◽

P. N. Richard Dekhuijzen ◽

...

Keyword(s):

Mechanical Ventilation ◽

Caspase 3 ◽

Toll Like Receptor ◽

Wild Type ◽

Toll Like Receptor 4 ◽

Ubiquitin Proteasome Pathway ◽

Ubiquitin Proteasome ◽

Proteasome Pathway ◽

Diaphragm Atrophy ◽

Deficient Mice

Background Mechanical ventilation induces diaphragm muscle atrophy, which plays a key role in difficult weaning from mechanical ventilation. The signaling pathways involved in ventilator-induced diaphragm atrophy are poorly understood. The current study investigated the role of Toll-like receptor 4 signaling in the development of ventilator-induced diaphragm atrophy. Methods Unventilated animals were selected for control: wild-type (n = 6) and Toll-like receptor 4 deficient mice (n = 6). Mechanical ventilation (8 h): wild-type (n = 8) and Toll-like receptor 4 deficient (n = 7) mice.Myosin heavy chain content, proinflammatory cytokines, proteolytic activity of the ubiquitin-proteasome pathway, caspase-3 activity, and autophagy were measured in the diaphragm. Results Mechanical ventilation reduced myosin content by approximately 50% in diaphragms of wild-type mice (P less than 0.05). In contrast, ventilation of Toll-like receptor 4 deficient mice did not significantly affect diaphragm myosin content. Likewise, mechanical ventilation significantly increased interleukin-6 and keratinocyte-derived chemokine in the diaphragm of wild-type mice, but not in ventilated Toll-like receptor 4 deficient mice. Mechanical ventilation increased diaphragmatic muscle atrophy factor box transcription in both wild-type and Toll-like receptor 4 deficient mice. Other components of the ubiquitin-proteasome pathway and caspase-3 activity were not affected by ventilation of either wild-type mice or Toll-like receptor 4 deficient mice. Mechanical ventilation induced autophagy in diaphragms of ventilated wild-type mice, but not Toll-like receptor 4 deficient mice. Conclusion Toll-like receptor 4 signaling plays an important role in the development of ventilator-induced diaphragm atrophy, most likely through increased expression of cytokines and activation of lysosomal autophagy.

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