Toll-like receptor 2 in promoting angiogenesis after acute ischemic injury

Xu,Yifei; Zhou,Ying; Lin,Haiyan; Hu,Haiyang; Wang,Yuxing; Xu,Geng

doi:10.3892/ijmm.2013.1240

Toll-like receptor 2 in promoting angiogenesis after acute ischemic injury

Authors:
- Yifei Xu
- Ying Zhou
- Haiyan Lin
- Haiyang Hu
- Yuxing Wang
- Geng Xu
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Affiliations: Department of Cardiology, The Second Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou, Zhejiang 310009, P.R. China
Published online on: January 11, 2013 https://doi.org/10.3892/ijmm.2013.1240
Pages: 555-560

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Abstract

Angiogenesis is an important mechanism that protects tissue against necrosis following acute ischemic injury. The aim of this study was to investigate whether the Toll-like receptor 2 (TLR2) signaling pathway is involved in angiogenesis following ischemic injury by cell migration and lymphocyte invasion assays in vitro, and a mouse model of hindlimb ischemia by ligation in vivo, respectively. To assess the potential role of TLR2 activation in endothelial cell permeability, HUVECs were pretreated with Pam3CSK4 and analyzed using wound repair and transwell assays. The results showed that the TLR2 agonist induced human umbilical vein endothelial cell (HUVEC) migration and increased the permeability of HUVECs to lymphocyte. The lymphocyte invasion of TLR2 knockout (TLR2-/-) mice was inhibited as compared to that of wild-type (WT) mice. In the mouse model of hindlimb ischemia by ligation, blood perfusion of operated limbs was significantly lower in TLR2-/- compared to WT mice, 7 and 14 days after ligation. TLR2-/- mice showed a decreased CD31 expression in ischemic gastrocnemius at 7 and 14 days after ligation, reduced interleukin-6 (IL-6) level and lowered tumor necrosis factor-α (TNF-α) levels. These findings demonstrated that TLR2 activation promotes cell migration, cell permeability and the lymphocyte invasion of endothelial cells. TLR2 activation promotes angiogenesis in vivo, which may be associated with the serum of TNF-α levels and IL-6 release.

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