Complement system activation in cardiac and skeletal muscle pathology: friend or foe?

Adv Exp Med Biol. 2013:735:207-18. doi: 10.1007/978-1-4614-4118-2_14.


A major goal in current cardiology practice is to determine optimal strategies for minimizing myocardial necrosis and optimizing cardiac repair following an acute myocardial infarction. Temporally regulated activation and suppression of innate immunity may be critical for achieving this goal. Extensive experimental data in various animal models have indicated that inhibiting complement activation offers protection to cardiac tissue after ischemia/reperfusion. However, the results of clinical studies using complement inhibitors (mainly at the C5 level) in patients with acute myocardial infarction have largely been disappointing. In cases in which complement activation participates in the initial events of muscle cell destruction, as in autoimmune myocarditis or autoimmune muscle disorders, inhibition of complement activation is expected to prove a successful treatment. In other pathologic conditions in which complement is recruited by degenerating or dying muscle cells, as in ischemia, the ideal approach is probably to modulate rather than abruptly blunt complement activation. Beneficial effects of complement action with regard to waste disposal, recruitment of stem cells, regeneration, angiogenesis, and better utilization of energy sources under hypoxic conditions may also prove important for successful disease treatment. Patient outcome after myocardial infarction almost certainly depend upon the combined activation of several distinct but potentially interrelated signaling pathways, suggesting that a combination of treatments targeted to different pathways should be the therapy of choice, and modulation of complement could be one of them.

Publication types

  • Review

MeSH terms

  • Animals
  • Complement Activation / physiology*
  • Heart Diseases / immunology
  • Heart Diseases / physiopathology*
  • Humans
  • Immunity, Innate
  • Muscle, Skeletal / physiology
  • Muscle, Skeletal / physiopathology
  • Muscular Diseases / immunology
  • Muscular Diseases / physiopathology*
  • Myocardium / metabolism
  • Myositis / physiopathology
  • Regeneration