标题:Endothelial tyrosine kinase receptor B prevents VE-cadherin cleavage and protects against atherosclerotic lesion development in ApoE-/- mice
作者:Jiang, Hong; Huang, Shuhong; Li, Xinyun; Li, Xian; Huang, Shanying; Zhang, Yun; Chen, Zhe-Yu
作者机构:[Jiang, Hong; Li, Xinyun; Huang, Shanying; Zhang, Yun] Shandong Univ, Chinese Minist Educ, Key Lab Cardiovasc Remodeling & Funct Res, Qilu Hosp, Jinan 更多
通讯作者:Chen, ZY
通讯作者地址:[Chen, ZY]Shandong Univ, Sch Med, Shandong Prov Key Lab Mental Disorders, Dept Neurobiol, Jinan, Shandong, Peoples R China.
来源:ONCOTARGET
出版年:2015
卷:6
期:31
页码:30640-30649
DOI:10.18632/oncotarget.5855
关键词:atherosclerosis; endothelial barrier dysfunction; brain-derived; neurotrophic factor; tyrosine kinase receptor B; vascular endothelial; cadherin; Pathology Section
摘要:Tyrosine kinase receptor B (TrkB) is a high-affinity receptor for brain-derived neurotrophic factor (BDNF). In addition to its nervous system functions, TrkB is also expressed in the aortic endothelium. However, the effects of endothelial TrkB signaling on atherosclerosis remained unknown. Immunofluorescence analysis revealed that TrkB expression is downregulated in the endothelium of atherosclerotic lesions from ApoE-/- mice compared with the atheroma-free aorta of WT mice. Endothelial TrkB knockdown led to increased lesion size, lipid deposition and inflammatory responses in the atherosclerotic lesions of the ApoE-/- mice compared with the control mice. Mechanistic studies showed that TrkB activation prevented VE-cadherin shedding by enhancing the interaction between vascular endothelial protein tyrosine phosphatase and VE-cadherin, maintaining VE-cadherin in a dephosphorylated state. Our data demonstrate that TrkB is an endothelial injury-response molecule in atherogenesis. Endothelial BDNF/TrkB signaling reduces VE-cadherin shedding and protects against atherosclerotic lesion development in ApoE-/- mice.
收录类别:SCOPUS;SCIE
WOS核心被引频次:5
Scopus被引频次:6
资源类型:期刊论文
原文链接:https://www.scopus.com/inward/record.uri?eid=2-s2.0-84945533973&doi=10.18632%2foncotarget.5855&partnerID=40&md5=e435dcff29c8b4e155f0b8dbf10c4774
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