title: α4β7 Integrin (LPAM-1) is upregulated at atherosclerotic lesions and is involved in atherosclerosis progression.
abstract: OBJECTIVE
  Integrin activation and lymphocyte migration to the vascular intima is a key event in early atherosclerosis. α4β7 integrin (LPAM-1) and its ligand, mucosal addressin cell adhesion molecule (MAdCAM-1) are known to play an important role in homing of activated lymphocytes to gut-associated lymphoid tissues. However, it is unclear whether α4β7 integrin is involved in the pathogenesis of atherosclerosis.
  
  
  METHODS
  The expressions of α4β7 integrin and its ligands in atherosclerosis plaques from 12 week high fat diet (HFD) fed ApoE(-/-) and C57BL/6 mice were examined using immunofluorescent and immunohistochemical assays, respectively. We also generated ApoE/β7 double deficient mice and compared atherosclerotic lesion development in β7(+/+)ApoE(-/-) and β7(-/-)ApoE(-/-) mice that were fed with HFD for 12 weeks.
  
  
  RESULTS
  We found an upregulation of α4β7 integrin and its ligands VCAM-1 and MAdCAM-1 at atherosclerosis plaques in Apolipoprotein E deficient (ApoE(-/-)) mice fed with HFD for 12 weeks. Over the 12 week HFD period, peripheral blood lymphocyte (PBL) expression of α4β7 integrin increased in parallel with aortic lesion size. A removal of α4β7 integrin by genetic deletion of the β7 chain in the ApoE(-/-) mouse resulted in a markedly decreased 12 week-HFD atherosclerotic plaque area. β7(-/-) ApoE(-/-) macrophages showed reduced acetylated and native LDL uptake and phagocytic activity, revealing possible roles for α4β7 at two distinct stages of macrophage dysfunction during atherogenesis. Finally, a reduced activity of integrin downstream signalling components focal adhesion kinase (FAK) and MAPK/ERK1/2 in macrophage indicates their possible engagement during α4β7 integrin signalling in atherosclerosis.
  
  
  CONCLUSIONS
  Together our results reveal a critical role of α4β7 in diet-induced atherosclerosis in mouse.
authors: Department of Vascular and Endovascular Surgery, Changzheng Hospital, Shanghai, China.
authors: Kangkang
authors: K
authors: Zhi
authors: Mengfan
authors: M
authors: Li
authors: Xiaoping
authors: X
authors: Zhang
authors: Zhiwei
authors: Z
authors: Gao
authors: Jun
authors: J
authors: Bai
authors: Yongfa
authors: Y
authors: Wu
authors: Sili
authors: S
authors: Zhou
authors: Maoquan
authors: M
authors: Li
authors: Lefeng
authors: L
authors: Qu
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015153:Blotting, Western; D015815:Cell Adhesion Molecules / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects; D018450:Disease Progression; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D039641:Integrin beta Chains / Q000235:genetics / Q000378:metabolism; D016023:Integrins / Q000235:genetics / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism / Q000493:pharmacokinetics; D017737:Macrophages, Peritoneal / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D009088:Mucoproteins; D010587:Phagocytosis; D010766:Phosphorylation; D058226:Plaque, Atherosclerotic / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D015815:Cell Adhesion Molecules; D039641:Integrin beta Chains; D016023:Integrins; D008077:Lipoproteins, LDL; C489082:Madcam1 protein, mouse; D009088:Mucoproteins; D019010:Vascular Cell Adhesion Molecule-1; C071777:integrin alpha4beta7; C091368:integrin beta7; D051416:Focal Adhesion Protein-Tyrosine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases