A vital role for complement in heart disease

Abstract

Heart diseases are common and significant contributors to worldwide mortality and morbidity. During recent years complement mediated inflammation has been shown to be an important player in a variety of heart diseases. Despite some negative results from clinical trials using complement inhibitors, emerging evidence points to an association between the complement system and heart diseases. Thus, complement seems to be important in coronary heart disease as well as in heart failure, where several studies underscore the prognostic importance of complement activation. Furthermore, patients with atrial fibrillation often share risk factors both with coronary heart disease and heart failure, and there is some evidence implicating complement activation in atrial fibrillation. Moreover, Chagas heart disease, a protozoal infection, is an important cause of heart failure in Latin America, and the complement system is crucial for the protozoa-host interaction. Thus, complement activation appears to be involved in the pathophysiology of a diverse range of cardiac conditions. Determination of the exact role of complement in the various heart diseases will hopefully help to identify patients that might benefit from therapeutic complement intervention.

Complement and contact system activation in acute congestive heart failure patients

“…Biomaterials as well as damaged endothelial cells, are potent complement activators and activate the contact system that intervenes in the inflammatory process releasing vasoactive kinins at the same time . Complement activation occurs in atrial fibrillation and the plasma levels of complement components may be used as prognostic indicators . Wei et al .…”

“…Biomaterials as well as damaged endothelial cells, are potent complement activators and activate the contact system that intervenes in the inflammatory process releasing vasoactive kinins at the same time [9][10][11]. Complement activation occurs in atrial fibrillation and the plasma levels of complement components may be used as prognostic indicators [12]. Wei et al [13] demonstrated that chronic myocardial stretch of a pure volume overload causes up-regulation of the kallikrein-kinin system, with an increase in interstitial fluid bradykinin that can mediate mast cell infiltration and extracellular matrix loss.…”

The alternative complement pathway is dysregulated in patients with chronic heart failure

“…Complement has also been demonstrated to play a role in myocardial ischemia-reperfusion damage and atherosclerosis formation 3,4 . The exact mechanisms of these detrimental effects are not fully elucidated, but likely involve tissue damage and activation of down-stream inflammatory processes 3,4 . The complement system can be activated through three different pathways: the classical, the lectin and the alternative pathway (AP) which all lead to formation of the central C3-and C5-convertases, and finally forms the terminal C5b-9 complement complex (TCC).…”

Compiling the Complement of Genes Implicated in Coronary Artery Disease

“…Experimental evidence suggests that the complement cascade may be involved in the development of atherosclerosis, 12,13 in part by promoting inflammation and phagocytosis of cholesterol crystals within the plaque. The activation of the complement system involves different pathways depending on the trigger (known as the classic, alternative, and lectin pathways), but all of them activate C3, which after cleavage to C3a and C3b, results in downstream activation of distal components of the cascade, including C6, C7, and C8.…”