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Leukocyte expression of complement C5a receptors exacerbates infarct size after myocardial reperfusion injury.
MedLine Citation:
PMID:  24935433     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
AIMS: Early reperfusion is mandatory for the treatment of acute myocardial infarction. This process, however, also induces additional loss of viable myocardium, called ischemia-reperfusion (IR) injury. Complement activation plays an important role in IR injury, partly through binding of C5a to its major receptor (C5aR). We investigated the role of C5aR on infarct size and cardiac function in a model for myocardial IR injury.
METHODS AND RESULTS: BALB/c (WT) mice and C5aR-/- mice underwent coronary occlusion for 30 minutes, followed by reperfusion. Infarct size, determined 24 hours after IR, was reduced in C5aR-/- mice compared to WT mice (28.5±2.1% vs. 35.7±2.5%, p=0.017). Bone marrow (BM) chimera experiments showed that this effect was due to absence of C5aR on circulating leukocytes, since a similar reduction in infarct size was observed in WT mice with C5aR-deficient BM cells (25.3±2.2% vs. 34.6±2.8%, p<0.05), but not in C5aR-/- mice with WT BM cells. Reduced infarct size was associated with fewer neutrophils, T cells and macrophages in the infarcted area 24 hours after IR in C5aR-/- mice, and also with lower levels of Caspase-3/7 indicating less inflammation and apoptosis. Echocardiography 4 weeks after IR showed an improved ejection fraction in C5aR-/- mice (25.8±5.5% vs. 19.2±5.4%, p<0.001).
CONCLUSION: Absence of C5aR on circulating leukocytes reduces infarct size, is associated with reduced leukocyte infiltration and with less apoptosis in the infarcted myocardium, and improves cardiac function in a mouse model of myocardial IR injury. Selective blocking of C5aR might be a promising strategy to prevent myocardial IR injury.
Authors:
Vince C De Hoog; Leo Timmers; Amerik Van Duijvenvoorde; Saskia C A De Jager; Ben J Van Middelaar; Mirjam B Smeets; Trent M Woodruff; Pieter A Doevendans; Gerard Pasterkamp; C Erik Hack; Dominique P V De Kleijn
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-6-15
Journal Detail:
Title:  Cardiovascular research     Volume:  -     ISSN:  1755-3245     ISO Abbreviation:  Cardiovasc. Res.     Publication Date:  2014 Jun 
Date Detail:
Created Date:  2014-6-17     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0077427     Medline TA:  Cardiovasc Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.
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