Related Experiment Video
Updated: Dec 19, 2025
Delivery of Cardioactive Therapeutics in a Porcine Myocardial Infarction Model
Published on: February 10, 2023
Agrin Promotes Coordinated Therapeutic Processes Leading to Improved Cardiac Repair in Pigs
Andrea Baehr1,2, Kfir Baruch Umansky3, Elad Bassat3
1I Medizinische Klinik & Poliklinik, University Clinic Rechts der Isar, Technical University Munich, Germany (A.B., V.J., K.K., T.B., N.H., K.L.L., R.H., C.K.).
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.
