Systemic Inflammation Rapidly Induces Reversible Atrial Electrical Remodeling: The Role of Interleukin‐6–Mediated Changes in Connexin Expression

Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease

Iacopo Bertolozzi¹  Ujala Srivastava²  Mohamed Boutjdir²  Aleksander Dokollari³  Massimo Maccherini³  Gabriele Cevenini⁴  Pietro Enea Lazzerini⁵  Francesco Finizola⁵  Francesca Vanni⁵  Enrico Selvi⁵  Franco Laghi‐Pasini⁵  Beatrice Giabbani⁵  Pier Leopoldo Capecchi⁵  Mariarita Natale⁵  Nicola Migliacci⁵  Maurizio Acampa⁶ 

[1] Cardiology Intensive Therapy Unit Department of Internal Medicine Hospital of Carrara Italy;Cardiovascular Research Program VA New York Harbor Healthcare System Brooklyn, New York NY;Department of Cardiac Surgery University Hospital of Siena Italy;Department of Medical Biotechnologies University of Siena Italy;Department of Medical Sciences, Surgery and Neurosciences University of Siena Italy;Stroke Unit University Hospital of Siena Italy;

关键词: atrial electrical remodeling;    atrial fibrillation;    connexins;    interleukin‐6;    P‐wave indices;    systemic inflammation;   

DOI  :  10.1161/JAHA.118.011006

来源: DOAJ

【 摘 要 】

Background Systemic inflammation is a strong predictor of atrial fibrillation. A key role for electrical remodeling is increasingly recognized, and experimental data suggest that inflammatory cytokines can directly affect connexins resulting in gap‐junction dysfunction. We hypothesized that systemic inflammation, regardless of its origin, promotes atrial electric remodeling in vivo, as a result of cytokine‐mediated changes in connexin expression. Methods and Results Fifty‐four patients with different inflammatory diseases and elevated C‐reactive protein were prospectively enrolled, and electrocardiographic P‐wave dispersion indices, cytokine levels (interleukin‐6, tumor necrosis factor‐α, interleukin‐1, interleukin‐10), and connexin expression (connexin 40, connexin 43) were measured during active disease and after reducing C‐reactive protein by >75%. Moreover, peripheral blood mononuclear cells and atrial tissue specimens from an additional sample of 12 patients undergoing cardiac surgery were evaluated for atrial and circulating mRNA levels of connexins. Finally, in vitro effects of interleukin‐6 on connexin expression were studied in HL‐1 mouse atrial myocytes. In patients with active inflammatory diseases, P‐wave dispersion indices were increased but rapidly decreased within days when C‐reactive protein normalizes and interleukin‐6 levels decline. In inflammatory disease patients, both P‐wave dispersion indices and interleukin‐6 changes were inversely associated with circulating connexin levels, and a positive correlation between connexin expression in peripheral blood mononuclear cells and atrial tissue was demonstrated. Moreover, interleukin‐6 significantly reduced connexin expression in HL‐1 cells. Conclusions Our data suggest that regardless of specific etiology and organ localization, systemic inflammation, via interleukin‐6 elevation, rapidly induces atrial electrical remodeling by down‐regulating cardiac connexins. Although transient, these changes may significantly increase the risk for atrial fibrillation and related complications during active inflammatory processes.

【 授权许可】

Unknown