Agrin promotes coordinated therapeutic processes leading to improved cardiac repair in pigs
| Autor: | Renee Cohen-Rabi, Andrea Baehr, Kfir Baruch Umansky, Karl-Ludwig Laugwitz, Christian Kupatt, Rabea Hinkel, Nadja Hornaschewitz, Eldad Tzahor, Victoria Jurisch, Clemens C. Cyran, David Kain, Bartolo Ferraro, Tarik Bozoglu, Markus Krane, Olga Solyanik, Elad Bassat, Katharina Klett, Oliver Soehnlein |
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| Rok vydání: | 2019 |
| Předmět: |
Ischemic Heart Diseases
Cardiac function curve medicine.medical_specialty Swine medicine.medical_treatment Life quality Myocardial Infarction Ischemia Myocardial Reperfusion Injury 030204 cardiovascular system & hematology Revascularization Mice 03 medical and health sciences 0302 clinical medicine Fibrosis Physiology (medical) Internal medicine medicine Animals Humans Agrin Myocardial infarction 030304 developmental biology 0303 health sciences Therapeutic processes business.industry Recovery of Function medicine.disease Recombinant Proteins 3. Good health Heart failure Cardiac repair Cardiology Cardiology and Cardiovascular Medicine business Reperfusion injury |
| Zdroj: | Circulation |
| DOI: | 10.1101/854372 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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