Coronary Disease

Cardiac and Myocardial Ischemia

• Regarding inflammation as one mediator of I/R injury, experimental and clinical studies have shown that reperfusion after transient ischemia results in activation of endothelial cells, the contact and the complement system and attraction of neutrophils to the site of infarction (Wouters D et al. (2008) C1 inhibitor: just a serine protease inhibitor? New and old considerations on therapeutic applications of C1 inhibitor. Expert Opin Biol Ther 8(8):1225–40). 

• Complement-mediated ischemia-reperfusion injury: lessons learned from animal and clinical studies. Diepenhorst GM et al., (2009) complement-mediated ischemia-reperfusion injury: lessons learned from animal and clinical studies. Ann Surg 249(6):889–99).

• The complement system is a major component of innate immunity, which is involved in both recognition and response to pathogens (Walport MJ. (2001) Complement. Second of two parts. N Engl J Med 344(15):1140–4).

• It is further implicated in an increasing number of homeostatic and disease processes such as the immune complex catabolism, the clearance of dead and dying cells and the modulation of adaptive immune responses (Carroll MC. (2004)The complement system in regulation of adaptive immunity. Nat Immunol.  5(10):981–6. doi:10.1038/ni1113). 

• Three pathways can activate the complement cascade: the classical, the alternative, and the lectin pathway. After initiation, these three pathways converge at the level of cleavage and activation of complement component C3, which subsequently leads to the generation of the anaphylatoxins (C3a, C5a) and the membrane attack complex (MAC; C5b-9). (Panagiotou et al. 2018 The lectin pathway of Complement in Myocardial Ischemia/Reperfusion Injury—Review of Its Significance and the Potential Impact of Therapeutic Interference by C1 Esterase Inhibitor. Frontiers in Immunology | Volume 9 | Article 1151).