Junctional Ectopic Tachycardia Caused by Junctophilin-2 Expression Silencing Is Selectively Sensitive to Ryanodine Receptor Blockade.

Autor:	Yang Q; Division of Cardiology, Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina, USA.; Department of Cardiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China., Tadros HJ; Section of Cardiology, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA., Sun B; Division of Cardiology, Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina, USA., Bidzimou MT; Division of Cardiology, Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina, USA., Ezekian JE; Division of Cardiology, Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina, USA., Li F; Center for Drug Discovery and Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, USA., Ludwig A; Institut für Experimentelle und Klinische Pharmakologie, und Toxikologie, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany., Wehrens XHT; Section of Cardiology, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.; Cardiovascular Research Institute, Departments of Medicine (Cardiology), Molecular Physiology and Biophysics, and Neuroscience and Center for Space Medicine, Baylor College of Medicine, Houston, Texas, USA., Landstrom AP; Division of Cardiology, Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina, USA.; Department of Cell Biology, Duke University School of Medicine, Durham, North Carolina, USA.
Jazyk:	angličtina
Zdroj:	JACC. Basic to translational science [JACC Basic Transl Sci] 2023 Sep 27; Vol. 8 (12), pp. 1577-1588. Date of Electronic Publication: 2023 Sep 27 (Print Publication: 2023).
DOI:	10.1016/j.jacbts.2023.07.008
Abstrakt:	Junctional ectopic tachycardia (JET) is a potentially fatal cardiac arrhythmia. Hcn4:shJph2 mice serve as a model of nodal arrhythmias driven by ryanodine type 2 receptor (RyR2)-mediated Ca 2+ leak. EL20 is a small molecule that blocks RyR2 Ca 2+ leak. In a novel in vivo model of JET, Hcn4:shJph2 mice demonstrated rapid conversion of JET to sinus rhythm with infusion of EL20. Primary atrioventricular nodal cells demonstrated increased Ca 2+ transient oscillation frequency and increased RyR2-mediated stored Ca 2+ leak which was normalized by EL20. EL20 was found to be rapidly degraded in mouse and human plasma, making it a potential novel therapy for JET. Competing Interests: Dr Ezekian is supported by a National Institutes of Health (NIH) Clinical and Translational Science Award (UL1TR00255). Dr Ludwig is supported by the Cancer Prevention and Research Institute of Texas (RP160805) and the National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK121970). Dr Wehrens is supported by NIH grants R01-HL089598, R01-HL091947, R01-HL117641, and R01-HL147108 and the Quigley Endowed Chair in Cardiology; and is a co-founder and Scientific Advisory Board member of Elex Biotech, a drug development company focused on novel compounds for cardiac arrhythmia disorders and heart failure. Dr Landstrom is supported by the NIH (K08-HL136839 and R01-HL160654), the Doris Duke Charitable Foundation (CSDA-2020098), a Pediatric and Congenital Electrophysiology Society Paul C. Gillette Award, and the Mike Hogg Fund. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. (© 2023 The Authors.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu