Intermittent hypoxia causes NOX2-dependent remodeling of atrial connexins

BMC Cell Biology

Research

Eric C. Beyer¹  Abdelnaby Khalyfa¹  David Gozal¹  Joanna Gemel¹  Alex Gileles-Hillel²  Zihan Su³ 

[1] Department of Pediatrics, University of Chicago, 900 E. 57th St. KCBD 5152, 60637, Chicago, IL, USA;Present address: Department of Pediatrics, Hadassah-Hebrew University Medical Center, Mt. Scopus, Jerusalem, Israel;Present address: Williams College, Williamstown, MA, USA;

关键词: Intermittent hypoxia;    Obstructive sleep apnea;    Atrial fibrillation;    Gap junctions;    Connexin;   

DOI  :  10.1186/s12860-016-0117-5

来源: Springer

【 摘 要 】

BackgroundObstructive sleep apnea has been linked to the development of heart disease and arrhythmias, including atrial fibrillation. Since altered conduction through gap junction channels can contribute to the pathogenesis of such arrhythmias, we examined the abundance and distributions of the major cardiac gap junction proteins, connexin40 (Cx40) and connexin43 (Cx43) in mice treated with sleep fragmentation or intermittent hypoxia (IH) as animal models of the components of obstructive sleep apnea.ResultsWild type C57BL/6 mice or mice lacking NADPH 2 (NOX2) oxidase activity (gp91phox(−/Y)) were exposed to room air or to SF or IH for 6 weeks. Then, the mice were sacrificed, and atria and ventricles were immediately dissected. The abundances of Cx40 or Cx43 in atria and ventricles were unaffected by SF. In contrast, immunoblots showed that the abundance of atrial Cx40 and Cx43 and ventricular Cx43 were reduced in mice exposed to IH. qRT-PCR demonstrated significant reductions of atrial Cx40 and Cx43 mRNAs. Immunofluorescence microscopy revealed that the abundance and size of gap junctions containing Cx40 or Cx43 were reduced in atria by IH treatment of mice. However, no changes of connexin abundance or gap junction size/abundance were observed in IH-treated NOX2-null mice.ConclusionsThese results demonstrate that intermittent hypoxia (but not sleep fragmentation) causes reductions and remodeling of atrial Cx40 and Cx43. These alterations may contribute to the substrate for atrial fibrillation that develops in response to obstructive sleep apnea. Moreover, these connexin changes are likely generated in response to reactive oxygen species generated by NOX2.

【 授权许可】

CC BY   
© The Author(s). 2017