Document Detail


Activated protein C protects against myocardial ischemia/ reperfusion injury via inhibition of apoptosis and inflammation.
MedLine Citation:
PMID:  19372456     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: In spite of major advances in reperfusion therapy for patients presenting with acute coronary syndrome, long-term morbidity is still substantial. A limitation of initial treatment of myocardial ischemia is the lack of prevention of ischemia/reperfusion (I/R) injury. Activated protein C (APC), a crucial mediator in the coagulation process, plays a prominent role in the crosstalk between coagulation and inflammation and provides cytoprotective effects via inhibition of apoptosis and inflammation in several human and animal studies. METHODS AND RESULTS: APC was administered in an animal model for myocardial I/R. APC largely inhibited early myocardial I/R injury after varying reperfusion times, an effect that was absent on administration of heparin, a nonspecific anticoagulant agent. The protective effects of APC were absent in case of absence or blockade of protease activated receptor-1 (PAR-1), indicating a critical role for PAR-1 in this process. Furthermore, we showed a strong antiapoptotic effect of APC in the early phase of reperfusion combined with an antiinflammatory effect at an early stage (IL-6), as well as at a later stage (leukocyte infiltration). CONCLUSIONS: APC exerts strong protective effects on early myocardial I/R injury, primarily via inhibition of apoptosis and inflammation, which are regulated via PAR-1.
Authors:
Sarah T B G Loubele; C Arnold Spek; Peter Leenders; René van Oerle; Hella L Aberson; Karly Hamulyák; Gary Ferrell; Charles T Esmon; Henri M H Spronk; Hugo ten Cate
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-04-16
Journal Detail:
Title:  Arteriosclerosis, thrombosis, and vascular biology     Volume:  29     ISSN:  1524-4636     ISO Abbreviation:  Arterioscler. Thromb. Vasc. Biol.     Publication Date:  2009 Jul 
Date Detail:
Created Date:  2009-06-18     Completed Date:  2009-07-15     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9505803     Medline TA:  Arterioscler Thromb Vasc Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1087-92     Citation Subset:  IM    
Affiliation:
Department of Internal Medicine, Laboratory for Clinical Thrombosis and Haemostasis, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, The Netherlands. sarah.loubele@bioch.unimaas.nl
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MeSH Terms
Descriptor/Qualifier:
Animals
Anticoagulants / administration & dosage*
Apoptosis / drug effects*,  immunology
Gene Expression Regulation
Inflammation / physiopathology,  prevention & control
Male
Mice
Mice, Knockout
Myocardial Reperfusion Injury / immunology,  physiopathology,  prevention & control*
Protein C / administration & dosage*
Receptor, PAR-1 / drug effects,  physiology
Chemical
Reg. No./Substance:
0/Anticoagulants; 0/Protein C; 0/Receptor, PAR-1

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


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