Angiogenesis mediated by toll-like receptor 4 in ischemic neural tissue

Chang He, Yuying Sun, Xiangrong Ren, Qing Lin, Xiao Hu, Xi Huang, Shao Bo Su, Yizhi Liu, Xialin Liu

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


Objective-: Activation of the immune system via toll-like receptors (TLRs) is implicated in atherosclerosis, microvascular complications, and angiogenesis. However, the involvement of TLRs in inflammation-associated angiogenesis in ischemic neural tissue has not been investigated. The goal of this study is to determine the role of TLR4 signaling in oxygen-induced neovascularization in retina, a neural tissue. METHODS AND RESULTS-: In oxygen-induced retinopathy model, we found that retinal neovascularization was significantly attenuated in TLR4 mice. The further study revealed that the absence of TLR4 led to downregulation of proinflammatory factors in association with the attenuated activation of glia in the ischemic retina, which was also associated with reduced expression of high-mobility group box-1, an endogenous ligand for TLR4. The application of high-mobility group box-1 to the ischemic retina promoted the production of proinflammatory factors in wild-type but not TLR4 mice. High-mobility group box-1 treatment in vitro also significantly promoted the production of proinflammatory factors in retinal glial cells from wild-type mice, but much less from TLR4 mice. CONCLUSION-: Our results suggest that the release of high-mobility group box-1 in ischemic neural tissue initiates TLR4-dependent responses that contribute to neovascularization. These findings represented a previously unrecognized effect of TLR4 on angiogenesis in association with the activation of glia in ischemic neural tissue.

Original languageEnglish (US)
Pages (from-to)330-338
Number of pages9
JournalArteriosclerosis, thrombosis, and vascular biology
Issue number2
StatePublished - Feb 2013
Externally publishedYes


  • HMGB1
  • Toll-like receptor 4
  • angiogenesis
  • glial cells

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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