Leucocyte expression of complement C5a receptors exacerbates infarct size after myocardial reperfusion injury

De Hoog, Vince C., Timmers, Leo, Van Duijvenvoorde, Amerik, De Jager, Saskia C. A., Van Middelaar, Ben J., Smeets, Mirjam B., Woodruff, Trent M., Doevendans, Pieter A., Pasterkamp, Gerard, Hack, C. Erik and De Kleijn, Dominique P. V. (2014) Leucocyte expression of complement C5a receptors exacerbates infarct size after myocardial reperfusion injury. Cardiovascular Research, 103 4: 521-529. doi:10.1093/cvr/cvu153

Author De Hoog, Vince C.
Timmers, Leo
Van Duijvenvoorde, Amerik
De Jager, Saskia C. A.
Van Middelaar, Ben J.
Smeets, Mirjam B.
Woodruff, Trent M.
Doevendans, Pieter A.
Pasterkamp, Gerard
Hack, C. Erik
De Kleijn, Dominique P. V.
Title Leucocyte expression of complement C5a receptors exacerbates infarct size after myocardial reperfusion injury
Journal name Cardiovascular Research   Check publisher's open access policy
ISSN 1755-3245
Publication date 2014
Year available 2014
Sub-type Article (original research)
DOI 10.1093/cvr/cvu153
Open Access Status
Volume 103
Issue 4
Start page 521
End page 529
Total pages 9
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Collection year 2015
Language eng
Formatted abstract
Aims Early reperfusion is mandatory for the treatment of acute myocardial infarction. This process, however, also induces additional loss of viable myocardium, called ischaemia-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 min, followed by reperfusion. Infarct size, determined 24 h after IR, was reduced in C5aR-/- mice compared with WT mice (28.5±2.1 vs. 35.7±2.5%, P = 0.017). Bone marrow (BM) chimaera experiments showed that this effect was due to the absence of C5aR on circulating leucocytes, 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 withWTBM cells. Reduced infarct sizewas associated with fewer neutrophils, T cells, and macrophages in the infarcted area 24 h after IR in C5aR-/- mice, and also with lower levels of Caspase-3/7 indicating less inflammation and apoptosis. Echocardiography 4weeks after IR showed an improved ejection fraction in C5aR-/- mice (25.8±5.5 vs. 19.2±5.4%, P < 0.001).

Conclusion The absence of C5aR on circulating leucocytes reduces infarct size, is associated with reduced leucocyte 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.
Keyword Ischemia-reperfusion
Myocardial infarction
Infarct size
C5a receptor
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Biomedical Sciences Publications
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