Key result
Chronic A61603 increases length-dependent activation of contraction by ~25% in human engineered heart tissue.
Why the study?
Chronic stimulation of alpha1A-adrenergic receptors mediates therapeutic effects in animal heart failure models, but its effects in human cardiomyocytes required investigation.
Does chronic α1A-adrenergic receptor stimulation with A61603 improve length-dependent activation in human engineered heart tissue?
Does chronic α1A-adrenergic receptor stimulation with A61603 improve length-dependent activation in human engineered heart tissue?
Effect estimate: 25% increase
Absolute Event Rate: 117% vs 93%
p-value: p=0.035
Chronic stimulation of the α1A-adrenergic receptor with A61603 increases length-dependent activation in human engineered heart tissue, suggesting a potential therapeutic mechanism for heart failure.
May support α1A-AR agonism in engineered tissue; leaves open clinical translation in heart failure.
Chronic stimulation of α 1A -adrenergic receptors (α 1A -ARs) is known to mediate therapeutic effects in animal heart failure models. To investigate the effects of chronic α 1A -AR stimulation in human cardiomyocytes, we tested engineered heart tissue (EHT) created with iPSC-derived cardiomyocytes. RNA-seq analysis confirmed human EHT expressed α 1A -ARs. Chronic (2 wk) α 1A -AR stimulation with A61603 (10 nM) increased length-dependent activation (LDA) of contraction. Chronic α 1A -AR stimulation might be beneficial for treating human heart failure by restoring LDA.
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Rupert et al. (2023) studied Heart failure (in vitro model) (n=14). A61603 (α1A-adrenergic receptor agonist) vs. Vehicle was evaluated on Length-dependent activation (LDA) of contraction (% of initial) (25% increase, p=0.035). Chronic treatment with the α1A-adrenergic receptor agonist A61603 increased length-dependent activation of contraction by 25% compared to vehicle in human engineered heart tissue.
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