FEBS Open Bio (Feb 2023)

Upregulation of HMGB1 promotes vascular dysfunction in the soft palate of patients with obstructive sleep apnea via the TLR4/NF‐κB/VEGF pathway

  • Tiantian Su,
  • Cong Li,
  • Yu Zhang,
  • Lei Yue,
  • Yuqin Chen,
  • Xiaoqiong Qian,
  • Song Shi

DOI
https://doi.org/10.1002/2211-5463.13533
Journal volume & issue
Vol. 13, no. 2
pp. 246 – 256

Abstract

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Obstructive sleep apnea (OSA) is characterized by the collapse of the soft palate in the upper airway, resulting in chronic intermittent hypoxia during sleep. Therefore, an understanding of the molecular mechanisms underlying pathophysiological dysfunction of the soft palate in OSA is necessary for the development of new therapeutic strategies. In the present study, we observed that high mobility group protein box 1 (HMGB1) was released by a large infiltration of macrophages in the soft palate of OSA patients. The toll‐like receptor 4/nuclear factor kappa B pathway was observed to be activated by the release of HMGB1, and this was accompanied by an increased expression of pro‐inflammatory factors, including tumor necrosis factor‐α and interleukin‐6. Importantly, increased expression of toll‐like receptor 4 was observed in endothelial cells, contributing to upregulation of the angiogenesis‐related factors vascular endothelial‐derived growth factor and matrix metalloproteinase 9. Moreover, we confirmed the effect of the HMGB1‐mediated toll‐like receptor 4/nuclear factor kappa B pathway on cell proliferation and angiogenesis in an in vitro cell model of human umbilical vein endothelial cells. We conclude that HMGB1 may be a potential therapeutic target for preventing angiogenesis and pathology in OSA.

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