ArticleInternational journal of molecular sciences2020
Conditional Up-Regulation of SERCA2a Exacerbates RyR2-Dependent Ventricular and Atrial Arrhythmias.
Article in International journal of molecular sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 16 citations in OpenAlex.
- Associations BetweenBiology · 2026Article
- The functional role of the circular RNA circCDR1as targeting SERCA2a in the progression of pathological cardiac hypertrophy and heart failure.Journal of translational medicine · 2026Article
- The interaction between sarcoplasmic reticulum and mitochondria: a novel mechanism for cardiac arrhythmia.Frontiers in physiology · 2026Review
- Targeting the Ubiquitin-Proteasome System in Atrial Fibrillation: Mechanistic Insights and Translational Perspectives.Current issues in molecular biology · 2025Review
- Gene and drug-mediated SERCA2a activation restores cardiac function and metabolic balance in diabetic mice.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2025Article
- LncRNA CCRR maintains CaScience China. Life sciences · 2024Article
- SERCA2 phosphorylation at serine 663 is a key regulator of CaNature communications · 2023Article
- Article
- Activin A directly impairs human cardiomyocyte contractile function indicating a potential role in heart failure development.Frontiers in cardiovascular medicine · 2022Article
- Effect of angiotensin receptor-neprilysin inhibitor on atrial electrical instability in atrial fibrillation.Frontiers in cardiovascular medicine · 2022Article
- Cellular Mechanisms Underlying the Low Cardiotoxicity of Istaroxime.Journal of the American Heart Association · 2021Article
- The YAP/SERCA2a signaling pathway protects cardiomyocytes against reperfusion-induced apoptosis.Aging · 2020Article
Corrections and comments
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Authors and funding
8 authors at 6 institutions in 1 country.
Funding
Abstract
Ryanodine receptor 2 (RyR2) and SERCA2a are two major players in myocyte calcium (Ca) cycling that are modulated physiologically, affected by disease and thus considered to be potential targets for cardiac disease therapy. However, how RyR2 and SERCA2a influence each others' activities, as well as the primary and secondary consequences of their combined manipulations remain controversial. In this study, we examined the effect of acute upregulation of SERCA2a on arrhythmogenesis by conditionally overexpressing SERCA2a in a mouse model featuring hyperactive RyR2s due to ablation of calsequestrin 2 (CASQ2). CASQ2 knock-out (KO) mice were crossbred with doxycycline (DOX)-inducible SERCA2a transgenic mice to generate KO-TG mice. In-vivo ECG studies have shown that induction of SERCA2a (DOX+) overexpression markedly exacerbated both ventricular and atrial arrhythmias in vivo, compared with uninduced KO-TG mice (DOX-). Consistent with that, confocal microscopy in both atrial and ventricular myocytes demonstrated that conditional upregulation of SERCA2a enhanced the rate of occurrence of diastolic Ca release events. Additionally, deep RNA sequencing identified 17 downregulated genes and 5 upregulated genes in DOX+ mice, among which Ppp1r13l, Clcn1, and Agt have previously been linked to arrhythmias. Our results suggest that conditional upregulation of SERCA2a exacerbates hyperactive RyR2-mediated arrhythmias by further elevating diastolic Ca release.
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Registered trials
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