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Thromb Haemost 2009; 102(03): 564-572
DOI: 10.1160/TH09-02-0103
Platelets and Blood Cells
Schattauer GmbH

Local complement activation triggers neutrophil recruitment to the site of thrombus formation in acute myocardial infarction

Klaus Distelmaier
1   Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria
,
Christopher Adlbrecht
1   Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria
,
Johannes Jakowitsch
1   Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria
,
Susanne Winkler
1   Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria
,
Daniela Dunkler
2   Section of Clinical Biometrics, Core Unit for Medical Statistics and Informatics, Medical University of Vienna, Vienna, Austria
,
Christopher Gerner
3   Department of Internal Medicine I, Division of Cancer Research, Medical University of Vienna, Vienna, Austria
,
Oswald Wagner
4   Department of Medical and Chemical Laboratory Diagnostics, Medical University of Vienna, Vienna, Austria
,
Irene M. Lang   *
1   Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria
,
Markus Kubicek   *
4   Department of Medical and Chemical Laboratory Diagnostics, Medical University of Vienna, Vienna, Austria
› Author AffiliationsFinancial support: This work was supported by the Austrian National Bank and “Oesterreichische Kardio-logische Gesellschaft”
Further Information

Publication History

Received: 18 February 2009

Accepted after major revision: 23 June 2009

Publication Date:
22 November 2017 (online)

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Summary

Atherosclerotic plaque rupture with subsequent mural thrombus formation is considered the main event compromising epicardial flow in acute myocardial infarction (AMI). However, the precise mechanisms underlying acute coronary occlusion are unknown.

We compared the proteomic profiles of systemic plasma and plasma derived from the site of thrombus formation of patients with AMI by two-dimensional gel electrophoresis and ELISA. We identified a local activation of the complement system, with selective accumulation of the complement activator Creactive protein (CRP) and the downstream complement effectors C3a and C5a. CRP in coronary thrombus co-localised with C1q and C3 immunoreactivities, suggesting classical complement activation. In vitro, coronary thrombus derived plasma enhanced neutrophil chemotaxis in a C5a dependent fashion. In vivo, neutrophil accumulation at the site of thrombus formation paralleled the time delay from symptom onset to first balloon inflation or aspiration, and was correlated with C5a and enzymatic infarct size. We present the first direct evidence for localised complement activation in acute coronary thrombi. Our data indicate that local complement effectors amplify the vascular occlusion process in AMI by enhanced neutrophil recruitment.

Keywords

Acute myocardial infarction - complement - neutrophils - proteomics - thrombosis

* Both authors contributed equally.


 

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