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C-reactive protein activates complement in infarcted human myocardium
Remco Nijmeijer1, Wim K Lagrand, Yvonne T P Lubbers
1Institute for Cardiovascular Research, Vrije Universiteit Medical Center, Amsterdam, The Netherlands.
Insights
C-reactive protein (CRP) activates complement in heart attack tissue, increasing inflammation. This CRP-mediated complement activation is significantly more pronounced in heart attacks over 12 hours old.
Area of Science:
- Cardiovascular Science
- Immunology
- Pathology
Background:
- Circulating C-reactive protein (CRP) is a known cardiovascular risk marker.
- Previous studies suggest CRP may enhance inflammation in ischemic myocardium by activating the complement system.
- Co-localization of CRP and activated complement has been observed in human infarcted myocardium.
Purpose of the Study:
- To determine if CRP activates complement within infarcted human myocardium.
- To investigate the relationship between CRP-mediated complement activation and the duration of myocardial infarction.
Main Methods:
- Analysis of myocardial tissue samples from 56 patients deceased from acute myocardial infarction.
- Immunohistochemistry to assess CRP-mediated complement activation.
- Measurement of complement, CRP, and CRP-complement complexes in heart tissue homogenates.
Main Results:
- Infarctions older than 12 hours showed significantly greater deposition of complement and CRP compared to younger infarcts.
- Tissues from older infarcts contained higher levels of CRP, activated complement, and CRP-complement complexes.
- Levels of CRP-complement complexes correlated significantly with CRP and complement concentrations and deposition extent.
Conclusions:
- CRP appears to enhance local inflammatory reactions in human myocardial infarcts.
- This enhancement is particularly evident in infarcts exceeding 12 hours in duration.
- CRP-mediated complement activation plays a role in the inflammatory process of established myocardial infarction.
Abstract:
Circulating levels of C-reactive protein (CRP) constitute a cardiovascular risk marker. Immunohistochemical studies have revealed co-localization of CRP and activated complement in human infarcted myocardium suggesting CRP to enhance inflammation in ischemic myocardium by inducing local complement activation. The aim was to establish whether CRP activates complement in infarcted human myocardium and to assess the relationship between this activation and the duration of infarction. Myocardial tissue samples from 56 patients that had died from acute myocardial infarction were evaluated. Specimens were taken from infarcted as well as noninfarcted sites of the heart. CRP-mediated complement activation was assessed by immunohistochemistry and by measuring levels of complement, CRP, and CRP-complement complexes, specific markers for CRP-mediated activation, in homogenates of the heart. Infarctions of 12 hours to 5 days had significantly more extensive depositions of complement and CRP and contained significantly more CRP, activated complement, and CRP-complement complexes than infarctions that were less than 12 hours old. Levels of CRP complexes correlated significantly with CRP and complement concentrations in the infarctions, as well as with the extent of complement and CRP depositions as measured via immunohistochemistry. Specific activation products of CRP-mediated activation of complement are increased in infarcts of more than 12 hours in duration and correlate with the extent of complement depositions. Hence, CRP seems to enhance local inflammatory reactions ensuing in human myocardial infarcts of more than 12 hours duration.