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- Title
Glycation of Tie-2 Inhibits Angiopoietin-1 Signaling Activation and Angiopoietin-1-Induced Angiogenesis.
- Authors
Zhou, Haiyan; Chen, Tangting; Li, Yongjie; You, Jingcan; Deng, Xin; Chen, Ni; Li, Tian; Zheng, Youkun; Li, Rong; Luo, Mao; Wu, Jianbo; Wang, Liqun
- Abstract
The impairment of the angiopoietin-1 (Ang-1)/Tie-2 signaling pathway has been thought to play a critical role in diabetic complications. However, the underlying mechanisms remain unclear. The present study aims to investigate the effects of Tie-2 glycation on Ang-1 signaling activation and Ang-1-induced angiogenesis. We identified that Tie-2 was modified by advanced glycation end products (AGEs) in aortae derived from high fat diet (HFD)-fed mice and in methylglyoxal (MGO)-treated human umbilical vein endothelial cells (HUVECs). MGO-induced Tie-2 glycation significantly inhibited Ang-1-evoked Tie-2 and Akt phosphorylation and Ang-1-regulated endothelial cell migration and tube formation, whereas the blockade of AGE formation by aminoguanidine remarkably rescued Ang-1 signaling activation and Ang-1-induced angiogenesis in vitro. Furthermore, MGO treatment markedly increased AGE cross-linking of Tie-2 in cultured aortae ex vivo and MGO-induced Tie-2 glycation also significantly decreased Ang-1-induced vessel outgrow from aortic rings. Collectively, these data suggest that Tie-2 may be modified by AGEs in diabetes mellitus and that Tie-2 glycation inhibits Ang-1 signaling activation and Ang-1-induced angiogenesis. This may provide a novel mechanism for Ang-1/Tie-2 signal dysfunction and angiogenesis failure in diabetic ischaemic diseases.
- Subjects
RECEPTOR for advanced glycation end products (RAGE); NEOVASCULARIZATION; ANGIOPOIETIN-1; AORTA; ADVANCED glycation end-products; HIGH-fat diet; UMBILICAL veins; ENDOTHELIAL cells
- Publication
International Journal of Molecular Sciences, 2022, Vol 23, Issue 13, p7137
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms23137137