Key result
Tachypacing reduced Cx43 expression via a miR-1-dependent mechanism in iPSC-CMs, and anti-miR-1 treatment restored Cx43 expression, enhanced Na+ currents, and synchronized electrical activity.
Why the study?
Arrhythmic diseases are associated with decreased Cx43 expression at intercalated discs and translocation to lateral membranes, but the underlying mechanisms remain unclear.
Does anti-miR-1 treatment restore Cx43 expression and improve electrical and Ca2+ signaling properties in tachypaced induced pluripotent stem cell-derived cardiomyocytes?
Does anti-miR-1 treatment restore Cx43 expression and improve electrical and Ca2+ signaling properties in tachypaced induced pluripotent stem cell-derived cardiomyocytes?
Anti-miR-1 treatment restores connexin-43 expression and normalizes electrical and calcium signaling in tachypaced iPSC-derived cardiomyocytes, highlighting miR-1 as a potential therapeutic target for arrhythmogenic remodeling.
Leaves open miR-1 inhibition for arrhythmogenic remodeling; requires in vivo and clinical validation before therapeutic consideration.
A common pathophysiological characteristic of arrhythmic diseases is the disruption of electrical signal transmission across the heart causing life-threatening rhythm disorders. These conditions are associated with decreased expression of connexin-43 (Cx43) at intercalated discs and its translocation to the lateral membranes, however, the underlying mechanisms remain unclear. Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) offer a model for studying these pathophysiological processes. Here, we tested the hypothesis that chronic stress, usually preceding arrhythmic developments, modulates Cx43 expression. iPSC-CM were electrically stimulated at a normal rate and by tachypacing, and their electrical and Ca 2+ signaling properties were analyzed. Our data revealed that tachypacing significantly reduced Cx43 expression by a micro-RNA miR-1-dependent mechanism. Anti-miR-1 treatment restored Cx43 expression in conditions of stress, enhanced Na + currents, improved Ca 2+ propagation and synchronized electrical activity. These findings suggest miR-1 as a potential pharmacological target for mitigating arrhythmogenic remodeling and restoring robust electrical signal transmission in cardiomyocytes.
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Ke et al. (2025) studied Arrhythmogenic diseases. Tachypacing and Anti-miR-1 treatment vs. Normal rate electrical stimulation was evaluated on Cx43 expression, electrical and Ca2+ signaling properties. Tachypacing reduced Cx43 expression via a miR-1-dependent mechanism in iPSC-CMs, and anti-miR-1 treatment restored Cx43 expression, enhanced Na+ currents, and synchronized electrical activity.
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