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Updated: Jun 20, 2026
Improved Rodent Model of Myocardial Ischemia and Reperfusion Injury
Published on: March 7, 2022
Humanized cobra venom factor decreases myocardial ischemia-reperfusion injury
W Brian Gorsuch1, Benjamin J Guikema, David C Fritzinger
1Center for Experimental Therapeutics and Reperfusion Injury, Brigham and Women's Hospital, Harvard School of Medicine, 75 Francis Street, Boston, MA 02115, USA.
Insights
Recombinant humanized cobra venom factor (HC3-1496) protects the heart from ischemia-reperfusion injury by modulating complement activation. This novel anti-complement therapy shows potential for clinical use in treating cardiac conditions.
Area of Science:
- Immunology
- Cardiovascular Biology
- Complement System
Background:
- Cobra venom factor (CVF) activates the complement system and is used experimentally.
- CVF's clinical use is limited by immunogenicity.
- Humanized CVF (HC3-1496) has been developed as a potential therapeutic.
Purpose of the Study:
- To evaluate the efficacy of humanized CVF (HC3-1496) in protecting against myocardial ischemia-reperfusion (MI/R) injury.
- To investigate the mechanism of HC3-1496 action on the complement system in the context of MI/R.
Main Methods:
- Treatment of mice with recombinant humanized CVF (HC3-1496).
- Induction of myocardial ischemia-reperfusion (MI/R) injury.
- Assessment of cardiac function and C3 deposition in the myocardium.
- Analysis of complement component titers (C3, C5) and complement activation.
Main Results:
- HC3-1496 treatment protected mice from MI/R injuries, preserving cardiac function.
- C3 deposition in the myocardium was absent in HC3-1496 treated mice post-MI/R.
- HC3-1496 induced complement activation and C3 depletion but preserved C5 titers, suggesting it does not form a C5 convertase in mice.
Conclusions:
- Humanized CVF (HC3-1496) effectively protects the ischemic myocardium from reperfusion injury.
- HC3-1496 acts as a novel anti-complement therapy by depleting C3 without forming a C5 convertase.
- HC3-1496 demonstrates potential for clinical application in treating complement-mediated cardiac damage.
Abstract:
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.
