Complement factor 5 blockade reduces porcine myocardial infarction size and improves immediate cardiac function.

Area of Science:

• Cardiovascular Research
• Immunology
• Complement System Biology

Background:

• Complement factor 5 (C5) inhibition showed promise in animal models of myocardial infarction but failed in clinical trials due to antibody cross-reactivity issues.
• Different inhibitors used in animal versus clinical studies may explain the discrepancy.
• Coversin (OmCI) is a C5 inhibitor with known efficacy in pigs and humans.

Purpose of the Study:

• To investigate the efficacy of Coversin in reducing infarct size and improving ventricular function in a porcine model of myocardial infarction.
• To evaluate Coversin's impact on inflammatory markers and complement activation during myocardial reperfusion.

Main Methods:

• A porcine model of myocardial infarction was established by occluding the left anterior descending coronary artery, followed by reperfusion.
• Blindly randomized pigs received either Coversin or placebo, with Coversin infused after occlusion and throughout reperfusion.
• Infarct size was assessed using triphenyl tetrazolium chloride staining and magnetic resonance imaging; ventricular function was evaluated by echocardiography.

Main Results:

• Coversin significantly reduced myocardial infarction size by 39% (TTC) and 19% (MRI) compared to placebo.
• Treatment with Coversin improved systolic displacement (31%) and velocity (29%) in the ventricles.
• Coversin attenuated myocardial interleukin-1β levels and E-selectin expression, and inhibited plasma C5 activation and myocardial C5b-9 deposition.

Conclusions:

• Coversin effectively reduces infarct size and improves cardiac function in a porcine model of myocardial infarction by inhibiting C5.
• The study demonstrates Coversin's anti-inflammatory effects by reducing interleukin-1β and E-selectin.
• C5 inhibition should be reconsidered as a therapeutic strategy for myocardial infarction.