title: Focal Adhesion Kinase Promotes the Progression of Aortic Aneurysm by Modulating Macrophage Behavior.
abstract: Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease that is associated with persistent inflammation and extracellular matrix degradation. The molecular mechanisms underlying the macrophage-mediated progression of AAA remain largely unclear.
  
  
  
  We show that focal adhesion kinase (FAK) expression and activity are enhanced in macrophages that are recruited to AAA tissue. FAK potentiates tumor necrosis factor-α-induced secretion of matrix-degrading enzymes and chemokines by cultured macrophages. FAK also promotes macrophage chemotaxis. In mice, the administration of a FAK inhibitor that tempers local macrophage accumulation markedly suppresses the development and progression of chemically induced AAA.
  
  
  
  FAK plays a key role in macrophage behavior, which underlies the chronic progression of AAA. These findings provide insights into AAA progression and identify FAK as a novel therapeutic target.
authors.affiliation: From the Department of Surgery and Clinical Science, Yamaguchi University Graduate School of Medicine, Ube, Japan (T.H., K.Y., O.Y., K.U., N.M., K.H.); Graduate School of Health and Welfare, Yamaguchi Prefectural University, Japan (K.Y.); Department of Rehabilitation for the Movement Functions, Research Institute, National Rehabilitation Center for Persons with Disabilities, Tokorozawa, Japan (Y.S.).
authors.forename: Takasuke
authors.initials: T
authors.lastname: Harada
authors.affiliation: From the Department of Surgery and Clinical Science, Yamaguchi University Graduate School of Medicine, Ube, Japan (T.H., K.Y., O.Y., K.U., N.M., K.H.); Graduate School of Health and Welfare, Yamaguchi Prefectural University, Japan (K.Y.); Department of Rehabilitation for the Movement Functions, Research Institute, National Rehabilitation Center for Persons with Disabilities, Tokorozawa, Japan (Y.S.). yoshimko@yamaguchi-u.ac.jp.
authors.forename: Koichi
authors.initials: K
authors.lastname: Yoshimura
authors.affiliation: From the Department of Surgery and Clinical Science, Yamaguchi University Graduate School of Medicine, Ube, Japan (T.H., K.Y., O.Y., K.U., N.M., K.H.); Graduate School of Health and Welfare, Yamaguchi Prefectural University, Japan (K.Y.); Department of Rehabilitation for the Movement Functions, Research Institute, National Rehabilitation Center for Persons with Disabilities, Tokorozawa, Japan (Y.S.).
authors.forename: Osamu
authors.initials: O
authors.lastname: Yamashita
authors.affiliation: From the Department of Surgery and Clinical Science, Yamaguchi University Graduate School of Medicine, Ube, Japan (T.H., K.Y., O.Y., K.U., N.M., K.H.); Graduate School of Health and Welfare, Yamaguchi Prefectural University, Japan (K.Y.); Department of Rehabilitation for the Movement Functions, Research Institute, National Rehabilitation Center for Persons with Disabilities, Tokorozawa, Japan (Y.S.).
authors.forename: Koshiro
authors.initials: K
authors.lastname: Ueda
authors.affiliation: From the Department of Surgery and Clinical Science, Yamaguchi University Graduate School of Medicine, Ube, Japan (T.H., K.Y., O.Y., K.U., N.M., K.H.); Graduate School of Health and Welfare, Yamaguchi Prefectural University, Japan (K.Y.); Department of Rehabilitation for the Movement Functions, Research Institute, National Rehabilitation Center for Persons with Disabilities, Tokorozawa, Japan (Y.S.).
authors.forename: Noriyasu
authors.initials: N
authors.lastname: Morikage
authors.affiliation: From the Department of Surgery and Clinical Science, Yamaguchi University Graduate School of Medicine, Ube, Japan (T.H., K.Y., O.Y., K.U., N.M., K.H.); Graduate School of Health and Welfare, Yamaguchi Prefectural University, Japan (K.Y.); Department of Rehabilitation for the Movement Functions, Research Institute, National Rehabilitation Center for Persons with Disabilities, Tokorozawa, Japan (Y.S.).
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Sawada
authors.affiliation: From the Department of Surgery and Clinical Science, Yamaguchi University Graduate School of Medicine, Ube, Japan (T.H., K.Y., O.Y., K.U., N.M., K.H.); Graduate School of Health and Welfare, Yamaguchi Prefectural University, Japan (K.Y.); Department of Rehabilitation for the Movement Functions, Research Institute, National Rehabilitation Center for Persons with Disabilities, Tokorozawa, Japan (Y.S.).
authors.forename: Kimikazu
authors.initials: K
authors.lastname: Hamano
mesh_terms: D000818:Animals; D001012:Aorta, Abdominal / Q000201:enzymology* / Q000473:pathology; D017544:Aortic Aneurysm, Abdominal / Q000201:enzymology* / Q000473:pathology / Q000517:prevention & control; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D002633:Chemotaxis; D004195:Disease Models, Animal; D004789:Enzyme Activation; D051417:Focal Adhesion Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D047428:Protein Kinase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; C496051:Ptk2 protein, mouse; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse
keywords: aorta; aortic aneurysm; chemotaxis; inflammation; macrophage