Oncotarget

Research Papers: Pathology:

Probucol prevents atrial ion channel remodeling in an alloxan-induced diabetes rabbit model

Huaying Fu, Guangping Li, Changle Liu, Jian Li, Lijun Cheng, Wansong Yang, Gary Tse, Jichao Zhao and Tong Liu _

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Oncotarget. 2016; 7:83850-83858. https://doi.org/10.18632/oncotarget.13339

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Abstract

Huaying Fu1, Guangping Li1, Changle Liu1, Jian Li1, Lijun Cheng1, Wansong Yang1, Gary Tse2,3, Jichao Zhao4 and Tong Liu1

1 Department of Cardiology, Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular disease, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, People’s Republic of China

2 Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong, SAR, P.R. China

3 Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong, SAR, P.R. China

4 Auckland Bioengineering Institute, The University of Auckland, New Zealand

Correspondence to:

Tong Liu, email:

Guangping Li, email:

Keywords: diabetes mellitus; atrial fibrillation; alloxan-induced diabetes; atrial ionic remodeling; calcium current; Pathology Section

Received: June 30, 2016 Accepted: November 09, 2016 Published: November 14, 2016

Abstract

Diabetes mellitus (DM) increases the risk of developing atrial fibrillation (AF), but the molecular mechanisms of diabetes-induced atrial remodeling processes have not been fully characterized. The aim of this study was to examine the mechanisms underlying atrial ion channel remodeling in alloxan-induced diabetes model in rabbits. A total of 40 Japanese rabbits were randomly assigned to a control group (C), alloxan-induced diabetic group (DM), probucol-treated control group (Control-P), and probucol-treated diabetic group (DM-P). Using whole-cell voltage-clamp techniques, ICa,L, INa and action potential durations (APDs) were measured in cardiomyocytes isolated from the left atria in the four groups, respectively. In the DM group, increased Ica,L and decreased INa currents were reflected in prolonged APD90 and APD50 values. These changes were reversed in the DM-P group. In conclusion, probucol cured AF by alleviating the ion channel remodeling of atrial myocytes in the setting of diabetes and the promising therapeutic potential of anti-oxidative compounds in the treatment of AF warrants further study.


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