Paradoxical SERCA dysregulation contributes to atrial fibrillation in a model of diet-induced obesity DOI Creative Commons
Daniela Ponce‐Balbuena, Daniel J. Tyrrell, Carlos Cruz-Cortés

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Авг. 6, 2024

Abstract Obesity is a major risk factor for atrial fibrillation (AF) the most common serious cardiac arrhythmia, but molecular mechanisms underlying diet-induced AF remain unclear. In this study, we subjected mice to chronic high-fat diet and acute sympathetic activation (‘two-hit’ model) study by which obesity promotes AF. Surface electrocardiography revealed that synergize during intracardiac tachypacing induce At cellular level, adrenergic stimulation facilitate formation of delayed afterdepolarizations in myocytes, implicating altered Ca 2+ dynamics as cause We found does not alter expression -handling proteins atria, including sarcoplasmic reticulum -ATPase (SERCA), component beat-to-beat cycling heart. Paradoxically, reduces phospholamban phosphorylation, suggesting decreased SERCA activity, yet myocytes from obese showed significantly increased transient amplitude SERCA-mediated uptake. Adrenergic further increases affect reuptake mice. Transcriptomics analysis prompts upregulation neuronatin, protein has been implicated known stimulate activity. propose mechanism primes paradoxical activation, facilitates conversion through -induced release gain myocytes. Overall, links obesity, signaling, AF, targeting may prove effective treating obesity-induced

Язык: Английский

Paradoxical SERCA dysregulation contributes to atrial fibrillation in a model of diet-induced obesity DOI Creative Commons
Daniela Ponce‐Balbuena, Daniel J. Tyrrell, Carlos Cruz-Cortés

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Авг. 6, 2024

Abstract Obesity is a major risk factor for atrial fibrillation (AF) the most common serious cardiac arrhythmia, but molecular mechanisms underlying diet-induced AF remain unclear. In this study, we subjected mice to chronic high-fat diet and acute sympathetic activation (‘two-hit’ model) study by which obesity promotes AF. Surface electrocardiography revealed that synergize during intracardiac tachypacing induce At cellular level, adrenergic stimulation facilitate formation of delayed afterdepolarizations in myocytes, implicating altered Ca 2+ dynamics as cause We found does not alter expression -handling proteins atria, including sarcoplasmic reticulum -ATPase (SERCA), component beat-to-beat cycling heart. Paradoxically, reduces phospholamban phosphorylation, suggesting decreased SERCA activity, yet myocytes from obese showed significantly increased transient amplitude SERCA-mediated uptake. Adrenergic further increases affect reuptake mice. Transcriptomics analysis prompts upregulation neuronatin, protein has been implicated known stimulate activity. propose mechanism primes paradoxical activation, facilitates conversion through -induced release gain myocytes. Overall, links obesity, signaling, AF, targeting may prove effective treating obesity-induced

Язык: Английский

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