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

Autor:	De Hoog VC; Laboratory of Experimental Cardiology, Department of Cardiology UMC Utrecht, University Medical Center Utrecht, Heidelberglaan 100, Room G02.523, Utrecht 3584 CX, The Netherlands., Timmers L; Laboratory of Experimental Cardiology, Department of Cardiology UMC Utrecht, University Medical Center Utrecht, Heidelberglaan 100, Room G02.523, Utrecht 3584 CX, The Netherlands., Van Duijvenvoorde A; Laboratory of Experimental Cardiology, Department of Cardiology UMC Utrecht, University Medical Center Utrecht, Heidelberglaan 100, Room G02.523, Utrecht 3584 CX, The Netherlands., De Jager SC; Laboratory of Experimental Cardiology, Department of Cardiology UMC Utrecht, University Medical Center Utrecht, Heidelberglaan 100, Room G02.523, Utrecht 3584 CX, The Netherlands., Van Middelaar BJ; Laboratory of Experimental Cardiology, Department of Cardiology UMC Utrecht, University Medical Center Utrecht, Heidelberglaan 100, Room G02.523, Utrecht 3584 CX, The Netherlands., Smeets MB; Laboratory of Experimental Cardiology, Department of Cardiology UMC Utrecht, University Medical Center Utrecht, Heidelberglaan 100, Room G02.523, Utrecht 3584 CX, The Netherlands., Woodruff TM; School of Biomedical Sciences, The University of Queensland, Brisbane, Australia., Doevendans PA; Laboratory of Experimental Cardiology, Department of Cardiology UMC Utrecht, University Medical Center Utrecht, Heidelberglaan 100, Room G02.523, Utrecht 3584 CX, The Netherlands., Pasterkamp G; Laboratory of Experimental Cardiology, Department of Cardiology UMC Utrecht, University Medical Center Utrecht, Heidelberglaan 100, Room G02.523, Utrecht 3584 CX, The Netherlands., Hack CE; Laboratory for Translational Immunology, UMC Utrecht, Utrecht, The Netherlands., De Kleijn DP; Laboratory of Experimental Cardiology, Department of Cardiology UMC Utrecht, University Medical Center Utrecht, Heidelberglaan 100, Room G02.523, Utrecht 3584 CX, The Netherlands Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands Surgery NUS and Cardiovascular Research Institute, NUHS, Singapore surdvp@nus.edu.sg.
Jazyk:	angličtina
Zdroj:	Cardiovascular research [Cardiovasc Res] 2014 Sep 01; Vol. 103 (4), pp. 521-9. Date of Electronic Publication: 2014 Jun 15.
DOI:	10.1093/cvr/cvu153
Abstrakt:	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 with WT BM cells. Reduced infarct size was 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 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: 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. (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.)
Databáze:	MEDLINE
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