Decreased bioavailability of hydrogen sulfide links vascular endothelium and atrial remodeling in atrial fibrillation.

Autor:	Watts M; The Departments of Medicine, And Molecular and Cellular Physiology and Center of Excellence for Cardiovascular Diseases & Sciences, Louisiana State University Health Sciences Center-Shreveport, Louisiana, United States., Kolluru GK; The Departments of Pathology, Molecular and Cellular Physiology, Cellular Biology and Anatomy And Center of Excellence for Cardiovascular Diseases & Sciences, Louisiana State University Health Sciences Center-Shreveport, Louisiana, United States., Dherange P; The Departments of Medicine, And Molecular and Cellular Physiology and Center of Excellence for Cardiovascular Diseases & Sciences, Louisiana State University Health Sciences Center-Shreveport, Louisiana, United States., Pardue S; The Departments of Pathology, Molecular and Cellular Physiology, Cellular Biology and Anatomy And Center of Excellence for Cardiovascular Diseases & Sciences, Louisiana State University Health Sciences Center-Shreveport, Louisiana, United States., Si M; The Departments of Cellular Biology and Anatomy and Center of Excellence for Cardiovascular Diseases & Sciences, Louisiana State University Health Sciences Center-Shreveport, Louisiana, United States; The Department of Biological Sciences, Southern Methodist University, Dallas, TX, USA., Shen X; The Departments of Pathology, Molecular and Cellular Physiology, Cellular Biology and Anatomy And Center of Excellence for Cardiovascular Diseases & Sciences, Louisiana State University Health Sciences Center-Shreveport, Louisiana, United States., Trosclair K; The Departments of Cellular Biology and Anatomy and Center of Excellence for Cardiovascular Diseases & Sciences, Louisiana State University Health Sciences Center-Shreveport, Louisiana, United States; The Department of Neurosurgery and Center of Excellence for Cardiovascular Diseases & Sciences, Louisiana State University Health Sciences Center-Shreveport, Louisiana, United States., Glawe J; The Departments of Pathology, Molecular and Cellular Physiology, Cellular Biology and Anatomy And Center of Excellence for Cardiovascular Diseases & Sciences, Louisiana State University Health Sciences Center-Shreveport, Louisiana, United States., Al-Yafeai Z; The Departments of Pathology, Molecular and Cellular Physiology, Cellular Biology and Anatomy And Center of Excellence for Cardiovascular Diseases & Sciences, Louisiana State University Health Sciences Center-Shreveport, Louisiana, United States., Iqbal M; The Departments of Medicine, And Molecular and Cellular Physiology and Center of Excellence for Cardiovascular Diseases & Sciences, Louisiana State University Health Sciences Center-Shreveport, Louisiana, United States., Pearson BH; The Departments of Pathology, Molecular and Cellular Physiology, Cellular Biology and Anatomy And Center of Excellence for Cardiovascular Diseases & Sciences, Louisiana State University Health Sciences Center-Shreveport, Louisiana, United States., Hamilton KA; The Departments of Cellular Biology and Anatomy and Center of Excellence for Cardiovascular Diseases & Sciences, Louisiana State University Health Sciences Center-Shreveport, Louisiana, United States., Orr AW; The Departments of Pathology, Molecular and Cellular Physiology, Cellular Biology and Anatomy And Center of Excellence for Cardiovascular Diseases & Sciences, Louisiana State University Health Sciences Center-Shreveport, Louisiana, United States., Glasscock E; The Departments of Cellular Biology and Anatomy and Center of Excellence for Cardiovascular Diseases & Sciences, Louisiana State University Health Sciences Center-Shreveport, Louisiana, United States; The Department of Biological Sciences, Southern Methodist University, Dallas, TX, USA., Kevil CG; The Departments of Pathology, Molecular and Cellular Physiology, Cellular Biology and Anatomy And Center of Excellence for Cardiovascular Diseases & Sciences, Louisiana State University Health Sciences Center-Shreveport, Louisiana, United States., Dominic P; The Departments of Medicine, And Molecular and Cellular Physiology and Center of Excellence for Cardiovascular Diseases & Sciences, Louisiana State University Health Sciences Center-Shreveport, Louisiana, United States. Electronic address: pdomi2@lsuhsc.edu.
Jazyk:	angličtina
Zdroj:	Redox biology [Redox Biol] 2021 Jan; Vol. 38, pp. 101817. Date of Electronic Publication: 2020 Dec 03.
DOI:	10.1016/j.redox.2020.101817
Abstrakt:	Oxidative stress drives the pathogenesis of atrial fibrillation (AF), the most common arrhythmia. In the cardiovascular system, cystathionine γ-lyase (CSE) serves as the primary enzyme producing hydrogen sulfide (H 2 S), a mammalian gasotransmitter that reduces oxidative stress. Using a case control study design in patients with and without AF and a mouse model of CSE knockout (CSE-KO), we evaluated the role of H 2 S in the etiology of AF. Patients with AF (n = 51) had significantly reduced plasma acid labile sulfide levels compared to patients without AF (n = 65). In addition, patients with persistent AF (n = 25) showed lower plasma free sulfide levels compared to patients with paroxysmal AF (n = 26). Consistent with an important role for H 2 S in AF, CSE-KO mice had decreased atrial sulfide levels, increased atrial superoxide levels, and enhanced propensity for induced persistent AF compared to wild type (WT) mice. Rescuing H 2 S signaling in CSE-KO mice by Diallyl trisulfide (DATS) supplementation or reconstitution with endothelial cell specific CSE over-expression significantly reduced atrial superoxide, increased sulfide levels, and lowered AF inducibility. Lastly, low H 2 S levels in CSE KO mice was associated with atrial electrical remodeling including longer effective refractory periods, slower conduction velocity, increased myocyte calcium sparks, and increased myocyte action potential duration that were reversed by DATS supplementation or endothelial CSE overexpression. Our findings demonstrate an important role of CSE and H 2 S bioavailability in regulating electrical remodeling and susceptibility to AF. (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze:	MEDLINE
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