Inhibitors of the complement system currently in development for cardiovascular disease

Controlled activation of the complement system is critical to the host-defense response of the immune system. Activated complement is responsible for the stimulation of a localized protective inflammatory response to either invading microorganisms or foreign molecules (toxins). However, the autologous activation of the complement system can have devastating consequences on many organ systems. This review discusses the various pathways involved in the activation of the complement system and the multiple levels of control established within the body to regulate activation. It also focuses on the role of complement activation in cardiovascular disease, especially myocardial ischemia and reperfusion injury as well as in cardiopulmonary bypass procedures. Lastly, this review also provides a comprehensive overview of both biologically derived proteins and chemically developed inhibitors of the complement system that range from those that are currently in the discovery stage to those that are in clinical development as novel therapeutic agents.