The activin receptor ligand trap ActRIIB:ALK4-Fc ameliorates cardiomyopathy induced by neuromuscular disease and diabetes.

Autor: Li J; Discovery Group, Acceleron Pharma Inc., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA., Fredericks M; Discovery Group, Acceleron Pharma Inc., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA., Tang M; Discovery Group, Acceleron Pharma Inc., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA., Cannell M; Discovery Group, Acceleron Pharma Inc., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA., Joshi S; Discovery Group, Acceleron Pharma Inc., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA., Kumar R; Discovery Group, Acceleron Pharma Inc., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA., Andre P; Discovery Group, Acceleron Pharma Inc., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA., Suragani RNVS; Discovery Group, Acceleron Pharma Inc., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
Jazyk: angličtina
Zdroj: FEBS letters [FEBS Lett] 2022 Dec; Vol. 596 (24), pp. 3145-3158. Date of Electronic Publication: 2022 Aug 29.
DOI: 10.1002/1873-3468.14464
Abstrakt: Cardiomyopathies are ascribed to a variety of etiologies, present with diverse clinical phenotypes, and lack disease-modifying treatments. Mounting evidence implicates dysregulated activin receptor signaling in heart disease and highlights inhibition of this pathway as a potential therapeutic target. Here, we explored the effects of activin ligand inhibition using ActRIIB:ALK4-Fc, a heterodimeric receptor fusion protein, in two mechanistically distinct murine models of cardiomyopathy. Treatment with ActRIIB:ALK4-Fc significantly improved systolic or diastolic function in cardiomyopathy induced by neuromuscular disease or diabetes mellitus. Moreover, ActRIIB:ALK4-Fc corrected Ca 2+ handling protein expression in diseased heart tissues, suggesting that activin signaling inhibition could alleviate cardiomyopathies in part by rebalancing aberrant intracellular Ca 2+ homeostasis-a common underlying pathomechanism in diverse heart diseases.
(© 2022 Federation of European Biochemical Societies.)
Databáze: MEDLINE
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