title: Tyrosine kinase receptor B protects against coronary artery disease and promotes adult vasculature integrity by regulating Ets1-mediated VE-cadherin expression.
abstract: OBJECTIVE
  Tyrosine kinase receptor B (TrkB) is a high-affinity receptor for brain-derived neurotrophic factor. In addition to its nervous system functions, TrkB is also expressed in the cardiovascular system. However, the association of TrkB and coronary artery disease (CAD) remains unknown. We investigated the role of TrkB in the development of CAD and its mechanism.
  
  
  RESULTS
  We performed a case-control study in 2 independent cohort of Chinese subjects and found -69C>G polymorphisms of TrkB gene significantly associated with CAD. TrkB -69C homozygotes, which corresponded to decreased TrkB expression by luciferase reporter assay, showed increased risk for CAD. Immunofluorescence analysis revealed that TrkB was expressed in the aortic endothelium in atherosclerotic lesions in humans and ApoE(-/-) mice. TrkB knockdown in the aortic endothelium resulted in vascular leakage in ApoE(-/-) mice. Mechanistic studies showed that TrkB regulated vascular endothelial cadherin (VE-cadherin) expression through induction and activation of Ets1 transcriptional factor. Importantly, TrkB activation attenuated proatherosclerotic factors induced-endothelial hyperpermeability in human vascular endothelial cells.
  
  
  CONCLUSIONS
  Our data demonstrate that TrkB protects endothelial integrity during atherogenesis by promoting Ets1-mediated VE-cadherin expression and plays a previously unknown protective role in the development of CAD.
authors: From the Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital (H.J., X.L., Y.Z.), and Department of Neurobiology, Shandong Provincial Key Laboratory of Mental Disorders, School of Medicine (S.H., X.L., Z.-Y.C), Shandong University, Jinan, Shandong, China.
authors: Hong
authors: H
authors: Jiang
authors: From the Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital (H.J., X.L., Y.Z.), and Department of Neurobiology, Shandong Provincial Key Laboratory of Mental Disorders, School of Medicine (S.H., X.L., Z.-Y.C), Shandong University, Jinan, Shandong, China.
authors: Shuhong
authors: S
authors: Huang
authors: From the Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital (H.J., X.L., Y.Z.), and Department of Neurobiology, Shandong Provincial Key Laboratory of Mental Disorders, School of Medicine (S.H., X.L., Z.-Y.C), Shandong University, Jinan, Shandong, China.
authors: Xinyun
authors: X
authors: Li
authors: From the Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital (H.J., X.L., Y.Z.), and Department of Neurobiology, Shandong Provincial Key Laboratory of Mental Disorders, School of Medicine (S.H., X.L., Z.-Y.C), Shandong University, Jinan, Shandong, China.
authors: Xian
authors: X
authors: Li
authors: From the Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital (H.J., X.L., Y.Z.), and Department of Neurobiology, Shandong Provincial Key Laboratory of Mental Disorders, School of Medicine (S.H., X.L., Z.-Y.C), Shandong University, Jinan, Shandong, China. zheyuchen@sdu.edu.cn zhangyun@sdu.edu.cn.
authors: Yun
authors: Y
authors: Zhang
authors: From the Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital (H.J., X.L., Y.Z.), and Department of Neurobiology, Shandong Provincial Key Laboratory of Mental Disorders, School of Medicine (S.H., X.L., Z.-Y.C), Shandong University, Jinan, Shandong, China. zheyuchen@sdu.edu.cn zhangyun@sdu.edu.cn.
authors: Zhe-Yu
authors: ZY
authors: Chen
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D044466:Asian People / Q000235:genetics; D050197:Atherosclerosis / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002199:Capillary Permeability; D016022:Case-Control Studies; D002681:China; D023921:Coronary Stenosis / Q000175:diagnosis / Q000201:enzymology* / Q000208:ethnology / Q000235:genetics / Q000517:prevention & control*; D003331:Coronary Vessels / Q000201:enzymology* / Q000473:pathology; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000201:enzymology; D020022:Genetic Predisposition to Disease; D006367:HeLa Cells; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D018345:Mice, Knockout; D010641:Phenotype; D011110:Polymorphism, Genetic; D065840:Protective Factors; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D050784:Proto-Oncogene Protein c-ets-1 / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D020813:Receptor, trkB; D012307:Risk Factors; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D001057:Apolipoproteins E; D015820:Cadherins; D008562:Membrane Glycoproteins; D011505:Protein-Tyrosine Kinases; D050784:Proto-Oncogene Protein c-ets-1; D020813:Receptor, trkB; D000099152:Cadherin 5; C494041:ETS1 protein, human; C064371:Ntrk2 protein, mouse; C000591259:tropomyosin-related kinase-B, human
keywords: brain-derived neurotrophic factor; cadherin 5; coronary artery disease