Complement-related molecular events in sepsis leading to heart failure.
Despite intensive ongoing research efforts, the mortality of patients with sepsis remains unacceptably high. A significant number of clinical trials have failed to produce sufficient therapeutic strategies despite showing promising results in animal models. So far, many studies have focused on deterioration of the humoral and cellular components of the immune system, the main cause of death in septic patients being multi-organ failure. However, not much is known about the effects of the complement system on parenchymal cells of organs such as the heart. Recently, septic cardiomyopathy has been recognized as one of the major complications during sepsis, often determining the clinical outcome. In this review, we describe molecular events which are thought to be related to cardiac dysfunction during sepsis. A special emphasis will be placed on the complement system, which generates powerful anaphylatoxins (such as C5a) and which has recently been associated with septic cardiomyopathy. Together with the impact on cardiac function of various cytokines we will provide a synopsis of the current knowledge regarding the pathophysiology underlying cardiac failure during sepsis with a special emphasis on C5a and C5aR.
Hoesel
Laszlo M
LM
Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Niederbichler
Andreas D
AD
Ward
Peter A
PA
D000818:Animals; D003165:Complement System Proteins / Q000502:physiology*; D016207:Cytokines / Q000502:physiology; D024243:HMGB1 Protein / Q000502:physiology; D006321:Heart / Q000503:physiopathology; D006333:Heart Failure / Q000209:etiology*; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D008263:Macrophage Migration-Inhibitory Factors / Q000502:physiology; D008565:Membrane Proteins / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement / Q000502:physiology; D018805:Sepsis / Q000150:complications*
C488033:C5AR1 protein, human; D016207:Cytokines; D024243:HMGB1 Protein; D008263:Macrophage Migration-Inhibitory Factors; D008565:Membrane Proteins; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement; D009569:Nitric Oxide; D003165:Complement System Proteins