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C-reactive protein and complement are important mediators of tissue damage in acute myocardial infarction
M Griselli1, J Herbert, W L Hutchinson
1Immunological Medicine Unit, Division of Medicine, Department of Histopathology, Hammersmith Hospital, London W12 ONN, United Kingdom.
Insights
Human C-reactive protein (CRP) worsens heart attack damage in rats by activating complement. Blocking complement reduces injury, highlighting CRP and complement as potential therapeutic targets for coronary heart disease.
Area of Science:
- Cardiovascular Science
- Immunology
- Biochemistry
Background:
- Myocardial infarction (heart attack) triggers an acute phase response in humans.
- C-reactive protein (CRP) and complement are deposited in heart infarcts, with high CRP linked to poor outcomes.
- Human CRP activates complement on damaged cells, unlike rat CRP.
Purpose of the Study:
- To investigate the role of human C-reactive protein (CRP) in myocardial infarction-induced injury.
- To determine if CRP exacerbates infarct size via complement activation.
- To explore complement activation as a therapeutic target for ischemic heart injury.
Main Methods:
- Induction of myocardial infarction in rats via coronary artery ligation.
- Injection of human CRP into rats post-infarction.
- Complement depletion using cobra venom factor.
- Measurement of infarct size.
Main Results:
- Human CRP injection increased infarct size by approximately 40% in rats.
- Complement depletion completely abolished the infarct-size-enhancing effect of human CRP.
- Complement depletion significantly reduced infarct size, even when initiated 2 hours after coronary ligation.
Conclusions:
- Human CRP and complement activation are key mediators of ischemic myocardial injury.
- Targeting CRP and complement pathways may offer therapeutic benefits for coronary heart disease.
- Complement activation contributes significantly to infarct expansion following myocardial infarction.
Abstract:
Myocardial infarction in humans provokes an acute phase response, and C-reactive protein (CRP), the classical acute phase plasma protein, is deposited together with complement within the infarct. The peak plasma CRP value is strongly associated with postinfarct morbidity and mortality. Human CRP binds to damaged cells and activates complement, but rat CRP does not activate complement. Here we show that injection of human CRP into rats after ligation of the coronary artery reproducibly enhanced infarct size by approximately 40%. In vivo complement depletion, produced by cobra venom factor, completely abrogated this effect. Complement depletion also markedly reduced infarct size, even when initiated up to 2 h after coronary ligation. These observations demonstrate that human CRP and complement activation are major mediators of ischemic myocardial injury and identify them as therapeutic targets in coronary heart disease.