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

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

FEBS letters (2022-08-04)
Jia Li, Maureen Fredericks, Mingxin Tang, Marishka Cannell, Sachindra Joshi, Ravindra Kumar, Patrick Andre, Rajasekhar N V S Suragani
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-Cav1.2 calcium channel Antibody, clone L57/46, clone L57/46, from mouse