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
Book Volume: 142
Pages Range: 868-881
Journal Issue: 9
DOI: 10.1161/CIRCULATIONAHA.119.045116
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.
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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