TY - JOUR
T1 - Probucol prevents atrial ion channel remodeling in an alloxaninduced diabetes rabbit model
AU - Fu, Huaying
AU - Li, Guangping
AU - Liu, Changle
AU - Li, Jian
AU - Cheng, Lijun
AU - Yang, Wansong
AU - Tse, Gary
AU - Zhao, Jichao
AU - Liu, Tong
N1 - Funding Information:
This work was supported by grants (30900618, 81270245, 81570298 to T.L.) from the National Natural Science Foundation of China, Tianjin Natural Science Foundation (16JCYBJC25000 to H.F., 16JCZDJC34900 to T.L.), the Croucher Foundation of Hong Kong (Diabetes Project Grant and Clinical Assistant Professorship to G.T.) and the Health Research Council of New Zealand (J.Z.).
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
KW - Alloxan-induced diabetes
KW - Atrial fibrillation
KW - Atrial ionic remodeling
KW - Calcium current
KW - Diabetes mellitus
KW - Pathology Section
UR - http://www.scopus.com/inward/record.url?scp=85007452370&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.13339
DO - 10.18632/oncotarget.13339
M3 - Article
C2 - 27863381
AN - SCOPUS:85007452370
VL - 7
SP - 83850
EP - 83858
JO - Oncotarget
JF - Oncotarget
IS - 51
ER -