Electrophysiological Abnormalities in VLCAD Deficient hiPSC-Cardiomyocytes Can Be Improved by Lowering Accumulation of Fatty Acid Oxidation Intermediates.

ABSTRACT: Patients with very long-chain acyl-CoA dehydrogenase deficiency (VLCADD) can present with life-threatening cardiac arrhythmias. The pathophysiological mechanism is unknown. We reprogrammed fibroblasts from one mildly and one severely affected VLCADD patient, into human induced pluripotent stem cells (hiPSCs) and differentiated these into cardiomyocytes (VLCADD-CMs). VLCADD-CMs displayed shorter action potentials (APs), more delayed afterdepolarizations (DADs) and higher systolic and diastolic intracellular Ca²⁺ concentration ([Ca²⁺]_i) than control CMs. The mitochondrial booster resveratrol mitigated the biochemical, electrophysiological and [Ca²⁺]_i changes in the mild but not in the severe VLCADD-CMs. Accumulation of potentially toxic

SUBMITTER: Knottnerus SJG 

PROVIDER: S-EPMC7177397 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature