Agrin Promotes Coordinated Therapeutic Processes Leading to Improved Cardiac Repair in Pigs
Baehr A, Umansky KB, Bassat E, Jurisch V, Klett K, Bozoglu T, Hornaschewitz N, Solyanik O, Kain D, Ferraro B, Cohen-Rabi R, Krane M, Cyran C, Soehnlein O, Laugwitz KL, Hinkel R, Kupatt C, Tzahor E (2020)
Publication Type: Journal article
Publication year: 2020
Journal
Book Volume: 142
Pages Range: 868-881
Journal Issue: 9
DOI: 10.1161/CIRCULATIONAHA.119.045116
Abstract
Background: Ischemic heart diseases are leading causes of death and reduced life quality worldwide. Although revascularization strategies significantly reduce mortality after acute myocardial infarction (MI), a large number of patients with MI develop chronic heart failure over time. We previously reported that a fragment of the extracellular matrix protein agrin promotes cardiac regeneration after MI in adult mice. Methods: To test the therapeutic potential of agrin in a preclinical porcine model, we performed ischemia-reperfusion injuries using balloon occlusion for 60 minutes followed by a 3-, 7-, or 28-day reperfusion period. Results: We demonstrated that local (antegrade) delivery of recombinant human agrin to the infarcted pig heart can target the affected regions in an efficient and clinically relevant manner. A single dose of recombinant human agrin improved heart function, infarct size, fibrosis, and adverse remodeling parameters 28 days after MI. Short-term MI experiments along with complementary murine studies revealed myocardial protection, improved angiogenesis, inflammatory suppression, and cell cycle reentry as agrin's mechanisms of action. Conclusions: A single dose of agrin is capable of reducing ischemia-reperfusion injury and improving heart function, demonstrating that agrin could serve as a therapy for patients with acute MI and potentially heart failure.
Involved external institutions
Weizmann Institute of Science
Israel (IL)
Technische Universität München (TUM)
Germany (DE)
Ludwig-Maximilians-Universität (LMU)
Germany (DE)
Deutsches Herzzentrum München
Germany (DE)
Israel (IL)
Technische Universität München (TUM)
Germany (DE)
Ludwig-Maximilians-Universität (LMU)
Germany (DE)
Deutsches Herzzentrum München
Germany (DE)
How to cite
APA:
Baehr, A., Umansky, K.B., Bassat, E., Jurisch, V., Klett, K., Bozoglu, T.,... Tzahor, E. (2020). Agrin Promotes Coordinated Therapeutic Processes Leading to Improved Cardiac Repair in Pigs. Circulation, 142(9), 868-881. https://doi.org/10.1161/CIRCULATIONAHA.119.045116
MLA:
Baehr, Andrea, et al. "Agrin Promotes Coordinated Therapeutic Processes Leading to Improved Cardiac Repair in Pigs." Circulation 142.9 (2020): 868-881.
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