Document Detail


Endothelial cell overexpression of fas ligand attenuates ischemia-reperfusion injury in the heart.
MedLine Citation:
PMID:  12576484     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Fas ligand (FasL) is a member of tumor necrosis factor family that induces apoptosis in target cells that express Fas. The function of FasL during inflammation remains controversial. In this study, we examined the role of vascular endothelial FasL during acute myocardial ischemia-reperfusion that is closely associated with inflammation. Transgenic mouse lines were established that overexpress human FasL on endothelium under the control of the vascular endothelial cadherin promoter. Expression of FasL transgene was detected at both mRNA and protein levels, and functional transgene-encoded FasL protein was specifically expressed on the surface of vascular endothelial cells. Transgenic mice developed normally and had normal hearts. When subjected to 30 min of myocardial ischemia and 72 h of reperfusion, myocardial infarct size was reduced by 42% in the transgenic mice compared with nontransgenic littermates (p < 0.05). Moreover, hemodynamic data demonstrated that transgenic hearts performed better following ischemia and reperfusion compared with nontransgenic hearts. Myocardial neutrophil infiltration was reduced by 54% after 6 h of reperfusion in transgenic hearts (p < 0.01). Neutrophil depletion prior to ischemia-reperfusion injury led to smaller infarcts that were not different between transgenic and nontransgenic mice, suggesting that endothelial FasL may attenuate ischemia-reperfusion injury by abating the inflammatory response. These results indicate that vascular endothelial FasL may exert potent anti-inflammatory actions in the setting of myocardial ischemia-reperfusion injury.
Authors:
Jiang Yang; Steven P Jones; Toshimitsu Suhara; James J M Greer; Paul D Ware; Nhan P Nguyen; Harris Perlman; David P Nelson; David J Lefer; Kenneth Walsh
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.     Date:  2003-02-07
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  278     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2003 Apr 
Date Detail:
Created Date:  2003-04-21     Completed Date:  2003-07-16     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  15185-91     Citation Subset:  IM    
Affiliation:
Molecular Cardiology, Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cadherins / genetics
Cell Line
Chemotaxis, Leukocyte
Endothelium, Vascular / metabolism*
Fas Ligand Protein
Heart / physiopathology
Hemodynamics
Membrane Glycoproteins / biosynthesis,  genetics,  physiology*
Mice
Mice, Transgenic
Myocardial Ischemia / pathology
Myocardial Reperfusion Injury / pathology,  prevention & control*
Neutrophils
Organ Size
Promoter Regions, Genetic
Grant Support
ID/Acronym/Agency:
AG-15052/AG/NIA NIH HHS; AG-17241/AG/NIA NIH HHS; AR40197/AR/NIAMS NIH HHS; DK43785/DK/NIDDK NIH HHS; HD-23681/HD/NICHD NIH HHS; HL-66957/HL/NHLBI NIH HHS; HL60849/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Cadherins; 0/FASLG protein, human; 0/Fas Ligand Protein; 0/Fasl protein, mouse; 0/Membrane Glycoproteins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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