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

Abstract

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 Ca2+ handling protein expression in diseased heart tissues, suggesting that activin signaling inhibition could alleviate cardiomyopathies in part by rebalancing aberrant intracellular Ca2+ homeostasis-a common underlying pathomechanism in diverse heart diseases.

• Authors: Jia Li, Maureen Fredericks, Mingxin Tang, Marishka Cannell, Sachindra Joshi, Ravindra Kumar, Patrick Andre, Rajasekhar N V S Suragani
• Journal: FEBS letters (FEBS Lett) Vol. 596 Issue 24 Pg. 3145-3158 (12 2022) ISSN: 1873-3468 [Electronic] England
• PMID: 35920165 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022 Federation of European Biochemical Societies.

Chemical References

• Activin Receptors
• Activins
• Ligands
• Activin Receptors, Type II

Topics

• Animals
• Mice
• Activin Receptors
• Activins
• Ligands
• Activin Receptors, Type II (genetics, metabolism, therapeutic use)
• Neuromuscular Diseases
• Cardiomyopathies (drug therapy, etiology)
• Diabetes Mellitus (drug therapy)