Role of the complement system in ischaemic heart disease: potential for pharmacological intervention.
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.