title: Periostin links mechanical strain to inflammation in abdominal aortic aneurysm.
abstract: OBJECTIVE
  Abdominal aortic aneurysms (AAAs) are characterized by chronic inflammation, which contributes to the pathological remodeling of the extracellular matrix. Although mechanical stress has been suggested to promote inflammation in AAA, the molecular mechanism remains uncertain. Periostin is a matricellular protein known to respond to mechanical strain. The aim of this study was to elucidate the role of periostin in mechanotransduction in the pathogenesis of AAA.
  
  
  RESULTS
  We found significant increases in periostin protein levels in the walls of human AAA specimens. Tissue localization of periostin was associated with inflammatory cell infiltration and destruction of elastic fibers. We examined whether mechanical strain could stimulate periostin expression in cultured rat vascular smooth muscle cells. Cells subjected to 20% uniaxial cyclic strains showed significant increases in periostin protein expression, focal adhesion kinase (FAK) activation, and secretions of monocyte chemoattractant protein-1 (MCP-1) and the active form of matrix metalloproteinase (MMP)-2. These changes were largely abolished by a periostin-neutralizing antibody and by the FAK inhibitor, PF573228. Interestingly, inhibition of either periostin or FAK caused suppression of the other, indicating a positive feedback loop. In human AAA tissues in ex vivo culture, MCP-1 secretion was dramatically suppressed by PF573228. Moreover, in vivo, periaortic application of recombinant periostin in mice led to FAK activation and MCP-1 upregulation in the aortic walls, which resulted in marked cellular infiltration.
  
  
  CONCLUSIONS
  Our findings indicated that periostin plays an important role in mechanotransduction that maintains inflammation via FAK activation in AAA.
authors.affiliation: Department of Surgery and Clinical Science, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Yamashita
authors.forename: Koichi
authors.initials: K
authors.lastname: Yoshimura
authors.forename: Ayako
authors.initials: A
authors.lastname: Nagasawa
authors.forename: Koshiro
authors.initials: K
authors.lastname: Ueda
authors.forename: Noriyasu
authors.initials: N
authors.lastname: Morikage
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Ikeda
authors.forename: Kimikazu
authors.initials: K
authors.lastname: Hamano
mesh_terms: D000368:Aged; D000818:Animals; D001012:Aorta, Abdominal / Q000378:metabolism* / Q000473:pathology*; D017544:Aortic Aneurysm, Abdominal / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D005260:Female; D051417:Focal Adhesion Kinase 1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D051381:Rats; D015854:Up-Regulation / Q000235:genetics
chemical_list: D015815:Cell Adhesion Molecules; D018932:Chemokine CCL2; D051417:Focal Adhesion Kinase 1; D020778:Matrix Metalloproteinase 2