Reduced infarct size after complement inhibition

Alice Gustavsen‘s PhD thesis shows reduced size of the myocardial infarction and improved ventricular function in pigs treated with the complement inhibitor Coversin.


MAIN RESULTS:

  1. Coversin substantially reduced infarct size compared to placebo in an experimental pig model of myocardial infarction.
  2. Coversin improved the systolic function of the left ventricle compared to placebo.
  3. By inhititing C5, coversin also reduced inflammation following myocardial infarction in pigs.

THESIS DEFENCE:

Thesis: Targeting innate immune pathways in acute infectious and sterile inflammation – The role of complement.
Candidate: Alice Gustavsen
Time: November 3, 2017 at 13:15
Place: University of Oslo, Domus Odontologica: Large Auditorium (A1.1001)
Link to university website (in Norwegian)


SUMMARY:

(3) The C5 inhibitor Coversin reduced the size of the myocardial infarction, improved left ventricular function, and attenuated interleukin-1β and E-selectin levels in pigs following reperfusion of an occluded left anterior descending coronary artery. Coversin was compared to placebo in 16 pigs randomized to the two treatment groups. The LAD occlusion lasted for 40 minutes, and coversin or placebo was infused 20 minutes after occlusion and throughout 240 minutes of reperfusion.

A chronically overactive innate immune system can damage the heart and other tissues. The complement is an important part of the innate immune system. Animal studies have shown that inhibition of the complement factor 5 (C5) can reduce myocardial infarction, but the same has not been found in human studies. However, diffent inhibitors have been used in animal and clinical studies. Coversin is a C5 inhibitor in both pigs and humans, and the researchers argue that there is a need to reconsider the use of complement inhibition in clinical myocardial infarction.

(1,2,4) The rest of Gustavsen’s PhD theses deals with complement inhibition in bacterial sepsis and severe antiphospholipid syndrome


REFERENCES:

(1) Nymo, S., Gustavsen, A., Nilsson, P. H., Lau, C., Espevik, T., & Mollnes, T. E. (2016). Human Endothelial Cell Activation by Escherichia coli and Staphylococcus aureus Is Mediated by TNF and IL-1β Secondarily to Activation of C5 and CD14 in Whole BloodThe Journal of Immunology196(5), 2293-2299.

(2) Gustavsen, A., Nymo, S., Landsem, A., Christiansen, D., Ryan, L., Husebye, H., Lau, C., Pischke, S. E., Lambris, J. D., Espevik, T., & Mollnes, T. E. (2016). Combined Inhibition of Complement and CD14 Attenuates Bacteria-Induced Inflammation in Human Whole Blood More Efficiently Than Antagonizing the Toll-like Receptor 4–MD2 ComplexThe Journal of infectious diseases214(1), 140-150.

(3) Pischke, S. E., Gustavsen, A., Orrem, H. L., Egge, K. H., Courivaud, F., Fontenelle, H., Despont, A., Bongoni, A. K., Rieben, R., Tønnessen, T. I., Nunn, M. A., Scott, H., Skulstad, H., Barratt-Due, A., & Mollnes, T. E. (2017). Complement factor 5 blockade reduces porcine myocardial infarction size and improves immediate cardiac functionBasic Research in Cardiology112(3), 20.

(4) Gustavsen, A., Skattum, L., Bergseth, G., Lorentzen, B., Floisand, Y., Bosnes, V., Mollnes, T. E., & Barratt-Due, A. (2017). Effect on mother and child of eculizumab given before caesarean section in a patient with severe antiphospholipid syndrome: A case report. Medicine96(11).