Humanized cobra venom factor decreases myocardial ischemia-reperfusion injury.
Cobra venom factor (CVF) is a complement activating protein in cobra venom, which functionally resembles C3b, and has been used for decades for decomplementation of serum to investigate the role of complement in many model systems of disease. The use of CVF for clinical practice is considered impractical because of immunogenicity issues. Humanization of CVF was recently demonstrated to yield a potent CVF-like molecule. In the present study, we demonstrate that mice treated with recombinant humanized CVF (HC3-1496) are protected from myocardial ischemia-reperfusion (MI/R) injuries with resultant preservation of cardiac function. Also, C3 deposition in the myocardium following MI/R was not observed following treatment with HC3-1496. HC3-1496 led to complement activation and depletion of C3, but preserved C5 titers. These data suggest, unlike CVF, HC3-1496 does not form a C5 convertase in the mouse, similar to recent studies in human sera/plasma. These results suggest that humanized CVF (HC3-1496) protects the ischemic myocardium from reperfusion injuries induced by complement activation and represents a novel anti-complement therapy for potential clinical use.
Gorsuch
W Brian
WB
Center for Experimental Therapeutics and Reperfusion Injury, Brigham and Women's Hospital, Harvard School of Medicine, 75 Francis Street, Boston, MA 02115, USA.
Guikema
Benjamin J
BJ
Fritzinger
David C
DC
Vogel
Carl-Wilhelm
CW
Stahl
Gregory L
GL
D000818:Animals; D003176:Complement C3 / Q000276:immunology; D003182:Complement C5 / Q000276:immunology; D004546:Elapid Venoms / Q000276:immunology*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000150:complications / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000150:complications / Q000276:immunology* / Q000503:physiopathology / Q000517:prevention & control*; D013318:Stroke Volume / Q000502:physiology; D016277:Ventricular Function, Left / Q000502:physiology
D003176:Complement C3; D003182:Complement C5; D004546:Elapid Venoms; C016310:cobra venom factor