PMID- 24260297
OWN - NLM
STAT- MEDLINE
DCOM- 20140707
LR  - 20240319
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 11
DP  - 2013
TI  - Periostin links mechanical strain to inflammation in abdominal aortic aneurysm.
PG  - e79753
LID - 10.1371/journal.pone.0079753 [doi]
LID - e79753
AB  - AIMS: 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. METHODS AND 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. CONCLUSION: Our findings indicated that periostin plays an 
      important role in mechanotransduction that maintains inflammation via FAK 
      activation in AAA.
FAU - Yamashita, Osamu
AU  - Yamashita O
AD  - Department of Surgery and Clinical Science, Yamaguchi University Graduate School 
      of Medicine, Ube, Japan.
FAU - Yoshimura, Koichi
AU  - Yoshimura K
FAU - Nagasawa, Ayako
AU  - Nagasawa A
FAU - Ueda, Koshiro
AU  - Ueda K
FAU - Morikage, Noriyasu
AU  - Morikage N
FAU - Ikeda, Yasuhiro
AU  - Ikeda Y
FAU - Hamano, Kimikazu
AU  - Hamano K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131119
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (Chemokine CCL2)
RN  - EC 2.7.10.2 (Focal Adhesion Kinase 1)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
SB  - IM
MH  - Aged
MH  - Animals
MH  - Aorta, Abdominal/*metabolism/*pathology
MH  - Aortic Aneurysm, Abdominal/genetics/*metabolism/*pathology
MH  - Cell Adhesion Molecules/genetics/*metabolism
MH  - Cells, Cultured
MH  - Chemokine CCL2/genetics/metabolism
MH  - Female
MH  - Focal Adhesion Kinase 1/genetics/metabolism
MH  - Humans
MH  - Inflammation/genetics/*metabolism/*pathology
MH  - Male
MH  - Matrix Metalloproteinase 2/genetics/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Muscle, Smooth, Vascular/metabolism/pathology
MH  - Rats
MH  - Up-Regulation/genetics
PMC - PMC3833967
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/11/22 06:00
MHDA- 2014/07/08 06:00
PMCR- 2013/11/19
CRDT- 2013/11/22 06:00
PHST- 2013/07/30 00:00 [received]
PHST- 2013/09/30 00:00 [accepted]
PHST- 2013/11/22 06:00 [entrez]
PHST- 2013/11/22 06:00 [pubmed]
PHST- 2014/07/08 06:00 [medline]
PHST- 2013/11/19 00:00 [pmc-release]
AID - PONE-D-13-31053 [pii]
AID - 10.1371/journal.pone.0079753 [doi]
PST - epublish
SO  - PLoS One. 2013 Nov 19;8(11):e79753. doi: 10.1371/journal.pone.0079753. 
      eCollection 2013.