title: Endothelial tyrosine kinase receptor B prevents VE-cadherin cleavage and protects against atherosclerotic lesion development in ApoE-/- mice.
abstract: 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.
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Neurobiology, Shandong Provincial Key Laboratory of Mental Disorders, School of Medicine, Shandong University, Jinan, Shandong, China.
authors.forename: Shuhong
authors.initials: S
authors.lastname: Huang
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Xinyun
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Neurobiology, Shandong Provincial Key Laboratory of Mental Disorders, School of Medicine, Shandong University, Jinan, Shandong, China.
authors.forename: Xian
authors.initials: X
authors.lastname: Li
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Shanying
authors.initials: S
authors.lastname: Huang
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Neurobiology, Shandong Provincial Key Laboratory of Mental Disorders, School of Medicine, Shandong University, Jinan, Shandong, China.
authors.forename: Zhe-Yu
authors.initials: ZY
authors.lastname: Chen
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics*; D050197:Atherosclerosis / Q000517:prevention & control*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism; D004730:Endothelium, Vascular / Q000473:pathology*; D007249:Inflammation / Q000276:immunology; D008055:Lipids; D008264:Macrophages / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D058226:Plaque, Atherosclerotic / Q000517:prevention & control*; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D020813:Receptor, trkB; D015398:Signal Transduction; D019108:Tight Junctions / Q000502:physiology; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D001057:Apolipoproteins E; D019208:Brain-Derived Neurotrophic Factor; D015820:Cadherins; D008055:Lipids; D008562:Membrane Glycoproteins; D011505:Protein-Tyrosine Kinases; D034741:RNA, Small Interfering; D020813:Receptor, trkB; D000099152:Cadherin 5; C000591259:tropomyosin-related kinase-B, human
keywords: Pathology Section; atherosclerosis; brain-derived neurotrophic factor; endothelial barrier dysfunction; tyrosine kinase receptor B; vascular endothelial cadherin