Details

Autor(en) / Beteiligte

• Baehr, Andrea
• Umansky, Kfir Baruch
• Bassat, Elad
• Jurisch, Victoria
• Klett, Katharina
• Bozoglu, Tarik
• Hornaschewitz, Nadja
• Solyanik, Olga
• Kain, David
• Ferraro, Bartolo
• Cohen-Rabi, Renee
• Krane, Markus
• Cyran, Clemens
• Soehnlein, Oliver
• Laugwitz, Karl Ludwig
• Hinkel, Rabea
• Kupatt, Christian
• Tzahor, Eldad

Titel

Agrin Promotes Coordinated Therapeutic Processes Leading to Improved Cardiac Repair in Pigs

Ist Teil von

• Circulation (New York, N.Y.), 2020-09, Vol.142 (9), p.868-881

Ort / Verlag

by the American College of Cardiology Foundation and the American Heart Association, Inc

Erscheinungsjahr

2020

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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.