ZFHX3 Knockdown Enhances Metabolic Distress in Atrial Myocytes Through Mitochondrial and Calcium Dysregulation: Mitigation by Trimetazidine.

ABSTRACT: Metabolic dysregulation in the heart plays a critical role in the pathogenesis of atrial fibrillation (AF), yet the underlying molecular mechanisms remain unclear. Loss-of-function variants in the zinc finger homeobox 3 gene (ZFHX3) increase AF risk by promoting structural and electrical remodeling. However, the role of ZFHX3 knockdown (KD) in cardiac metabolism has not been fully elucidated. This study investigated the impact of ZFHX3 KD on energy metabolism in atrial myocytes and assessed the therapeutic potential of trimetazidine (TMZ). Seahorse XFe24 extracellular flux analysis, bioluminescent assays, microplate enzyme activity assays, and Western blotting were used to study energy substrate (glucose and fatty acid) oxidation stress, intracellular lactate content,

SUBMITTER: Lkhagva B 

PROVIDER: S-EPMC12429405 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature