SMN-deficiency disrupts SERCA2 expression and intracellular Ca²⁺ signaling in cardiomyocytes from SMA mice and patient-derived iPSCs.

ABSTRACT: Spinal muscular atrophy (SMA) is a neurodegenerative disease characterized by loss of alpha motor neurons and skeletal muscle atrophy. The disease is caused by mutations of the SMN1 gene that result in reduced functional expression of survival motor neuron (SMN) protein. SMN is ubiquitously expressed, and there have been reports of cardiovascular dysfunction in the most severe SMA patients and animal models of the disease. In this study, we directly assessed the function of cardiomyocytes isolated from a severe SMA model mouse and cardiomyocytes generated from patient-derived IPSCs. Consistent with impaired cardiovascular function at the very early disease stages in mice, heart failure markers such as brain natriuretic peptide were significantly elevated. Functionally, cardiomyocyte relaxa

SUBMITTER: Khayrullina G 

PROVIDER: S-EPMC7206821 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature