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- W2777761407 abstract "Objective: The clinical efficacy of neuregulin (NRG), a ligand of the Her family receptors, is hindered by off-target exposure and requisite daily systemic infusions. We recently encapsulated NRG in a hydrogel (HG) for targeted and sustained myocardial delivery; beneficial results in a murine model of ischemic cardiomyopathy were clear. Here, we evaluate NRG-HG’s translational potential for myocardial regeneration and functional improvement in the clinical realm using a preclinical ovine model of ischemic cardiomyopathy. Methods: Male Dorset sheep (n=30) underwent baseline cardiac assessment with MRI and pressure-volume (PV) catheterization. Myocardial infarction (MI) was induced by ligating the 2 nd and 3 rd diagonal artery branches, and sheep were randomized to receive myocardial borderzone injection of 1mL saline, HG alone, NRG alone, or NRG-HG. Eight weeks post-infarction, repeat hemodynamic assessment was performed followed by tissue acquisition. A subset underwent sacrifice at 1 week for molecular analyses. Results: Analysis of myocardial borderzone 1-week post-infarction revealed NRG-HG augmented phosphorylated ErbB4, ErbB2, ERK, and histone h3 compared with all other groups. This marker activation suggests receptor activation, downstream signaling, and cardiac cell-cycle entry. At 8 weeks, NRG-HG significantly reduced scar size and augmented ventricular function (Table). There was no evidence of off-target NRG at 1 and 8 weeks, and no evidence of gel embolization or neurologic insult (by brain MRI) from intramyocardial hydrogel delivery. Conclusion: Targeted and sustained intramyocardial delivery of NRG with an engineered hydrogel platform triggers regeneration of mammalian heart muscle and augments ventricular function in a large animal model of ischemic cardiomyopathy. This novel, engineered delivery system realizes the true potential of NRG and its translation to clinical regenerative therapeutics." @default.
- W2777761407 created "2018-01-05" @default.
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- W2777761407 date "2015-11-10" @default.
- W2777761407 modified "2023-09-26" @default.
- W2777761407 title "Abstract 18952: A Novel Engineered Neuregulin-hydrogel System Regenerates Mammalian Heart Muscle and Enhances Ventricular Function in a Preclinical Ovine Model of Ischemic Cardiomyopathy" @default.
- W2777761407 doi "https://doi.org/10.1161/circ.132.suppl_3.18952" @default.
- W2777761407 hasPublicationYear "2015" @default.
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