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Role of the complement system in ischaemic heart disease: potential for pharmacological intervention
1Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Insights
The complement system contributes to heart damage after ischaemic heart disease (IHD). Inhibiting complement activation may reduce tissue injury and offers a potential therapeutic strategy for IHD patients.
Area of Science:
- Immunology
- Cardiovascular Medicine
- Pharmacology
Background:
- The complement system is a crucial part of innate immunity, defending against pathogens.
- Emerging evidence implicates complement activation in the pathophysiology of ischaemic heart disease (IHD).
- Complement deposition is observed in infarcted areas of the heart in experimental models and human patients.
Purpose of the Study:
- To review the role of the complement system in ischaemic heart disease (IHD).
- To explore the potential for pharmacological interventions targeting complement in IHD.
Main Methods:
- Review of experimental models of acute myocardial infarction (MI).
- Analysis of autopsy specimens from acute MI patients.
- Examination of preclinical studies on complement inhibition and depletion.
- Survey of current clinical trials for anticomplement therapies.
Main Results:
- Complement is selectively deposited in areas of myocardial infarction.
- Inhibition or depletion of complement components reduces tissue injury in animal models of MI.
- Several novel anticomplement therapies are under investigation and in clinical trials.
Conclusions:
- The complement system plays a significant role in the tissue damage associated with IHD.
- Targeting the complement system represents a promising therapeutic strategy for managing IHD.
- Further clinical investigation is needed to establish the efficacy of anticomplement therapies in humans.
Abstract:
The complement system is an innate, cytotoxic host defence system that normally functions to eliminate foreign pathogens. However, considerable evidence suggests that complement plays a key role in the pathophysiology of ischaemic heart disease (IHD). Experimental models of acute myocardial infarction (MI) and autopsy specimens taken from acute MI patients demonstrate that complement is selectively deposited in areas of infarction. Furthermore, inhibition of complement activation or depletion of complement components prior to myocardial reperfusion has been shown to reduce complement-mediated tissue injury in numerous animal models. IHD remains a leading cause of patient morbidity and mortality. Considerable effort in recent years has therefore been directed by biotechnology and pharmaceutical industries towards the development of novel, human complement inhibitors. Proposed anticomplement therapeutic strategies include the administration of naturally occurring or recombinant complement regulators, anticomplement monoclonal antibodies, and anticomplement receptor antagonists. Although data regarding the effectiveness of anticomplement therapy in humans is limited at present, a number of novel anticomplement therapeutic strategies are currently in clinical trials. The role of complement in IHD and potential for pharmacological intervention is reviewed.