Biology

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Elucidating the Role of Syntaxin-1A in Cardiac Excitation-Contraction Coupling and Hypertrophic Remodeling in the Adult Mouse Heart
(2024-03-16) Anser, Fahad; Tsushima, Robert G.
Syntaxin-1A (STX1A) is a member of the SNARE family which is recognized for its role in membrane exocytosis and ion-channel regulation. Although the physiological properties of STX1A has been assessed in many tissues, its role within the heart remains unelucidated. To address this, a cardiomyocyte specific STX1A knockout (KO) model was generated in adult C57BL/6J mice. Through utilization of both in vivo and in vitro approaches, STX1A haploinsufficiency was demonstrated to induce transient contractile dysfunction, a global electromechanical delay, and reduction in Ca2+ handling gene expression. The depressed cardiac function was supported by volumetric overload of the left-ventricle and cardiomyocyte/sarcomeric restructuring. Furthermore, pathological hypertrophy was observed as evident by the re-expression of fetal genes and left-ventricular fibrosis. Collectively, the results suggest an important role of STX1A in cardiac E-C coupling, whereby its KO impairs the heart’s electromechanical function and induces ventricular remodelling to compensate for the elevated hemodynamic volume overload.