Document Detail


Lack of Phospholipase A2 Receptor Increases Susceptibility to Cardiac Rupture after Myocardial Infarction.
MedLine Citation:
PMID:  24305469     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
RATIONALE: Recent evidence indicates that the biological effects of secretory phospholipase A2s (sPLA2) cannot be fully explained by their catalytic activities. A cell surface receptor for sPLA2 (PLA2 receptor 1 [PLA2R]) and its high affinity ligands (including sPLA2-IB, -IIE, and -X) are expressed in the infarcted myocardium.
OBJECTIVE: This study asked whether PLA2R might play a pathogenic role in myocardial infarction (MI), using mice lacking PLA2R (PLA2R(-/-)).
METHODS AND RESULTS: MI was induced by permanent ligation of the left coronary artery. PLA2R(-/-) mice exhibited higher rates of cardiac rupture after MI compared with PLA2R wild-type (PLA2R(+/+)) mice (46% vs. 21%, respectively, P = 0.015). PLA2R(-/-) mice had a 31% decrease in collagen content and a 45% decrease in the number of α-SMA-positive fibroblasts in the infarcted region compared with PLA2R(+/+) mice. PLA2R was primarily found in myofibroblasts in the infarcted region. PLA2R(-/-) myofibroblasts were impaired in collagen-dependent migration, proliferation and activation of focal adhesion kinase in response to sPLA2-IB. Binding of sPLA2-IB to PLA2R promoted migration and proliferation of myofibroblasts through functional interaction with integrin β1 independent of the catalytic activity of sPLA2-IB. In rescue experiments, the injection of PLA2R(+/+) myofibroblasts into the infarcted myocardium prevented post-MI cardiac rupture and reversed the decrease in collagen content in the infarcted region in PLA2R(-/-) mice.
CONCLUSIONS: PLA2R deficiency increased the susceptibility to post-MI cardiac rupture through impaired healing of the infarcted region. This might be partly explained by a reduction in integrin β1-mediated migratory and proliferative responses of PLA2R(-/-) myofibroblasts.
Authors:
Hideto Mishina; Kazuhiro Watanabe; Shun Tamaru; Yosuke Watanabe; Daisuke Fujioka; Soichiro Takahashi; Koji Suzuki; Takamitsu Nakamura; Jun-Ei Obata; Kenichi Kawabata; Yasunori Yokota; Osamu Inoue; Makoto Murakami; Kohji Hanasaki; Kiyotaka Kugiyama
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-12-4
Journal Detail:
Title:  Circulation research     Volume:  -     ISSN:  1524-4571     ISO Abbreviation:  Circ. Res.     Publication Date:  2013 Dec 
Date Detail:
Created Date:  2013-12-5     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0047103     Medline TA:  Circ Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Internal Medicine II, University of Yamanashi.
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