Antiarrhythmic effect of atorvastatin on autoimmune myocarditis is mediated by improving myocardial repolarization.
3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, or statins, are known to inhibit cholesterol biosynthesis and prevent inflammation and oxidative stress. To explore the effects of atorvastatin on inflammatory progression and major cardiac electrophysiological changes in myocarditis, we used an animal model of experimental autoimmune myocarditis (EAM). In this model, BALB/c mice were treated with atorvastatin and we evaluated the levels of inflammation markers and currents of ionic channels that contribute to the duration of action potential (APD) of ventricular myocytes. We demonstrated that atorvastatin treatment attenuated inflammatory infiltration and suppressed the increase in TNF-alpha and IFN-gamma levels in EAM mouse hearts. In the whole-cell patch-clamp experiment, ventricular cardiomyocyte APD was prolonged in EAM group, and atorvastatin blocked this change. We further found that atorvastatin attenuated the significant decrease in outward potassium currents in EAM myocytes. Our results suggested that atorvastatin may ameliorate EAM progression by reducing inflammatory cytokine level. Atorvastatin exerted the antiarrhythmic effects by selectively affecting cardiomyocyte ion channel activity and therefore improves myocardial repolarization.
Tang
Qizhu
Q
Department of Cardiology, Renmin Hospital of Wuhan University, 238 Jiefang Rd, Wuhan 430060, P.R. China. qzhtang@yahoo.com
Huang
Ji
J
Qian
Haiyan
H
Chen
Li
L
Wang
Teng
T
Wang
Haining
H
Shen
Difei
D
Wu
Hui
H
Xiong
Ran
R
D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000188:drug therapy*; D000069059:Atorvastatin; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology; D004195:Disease Models, Animal; D006321:Heart / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects; D006538:Heptanoic Acids / Q000627:therapeutic use*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009205:Myocarditis / Q000188:drug therapy* / Q000276:immunology; D009206:Myocardium / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D011758:Pyrroles / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D016276:Ventricular Function
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D015221:Potassium Channels; D011758:Pyrroles; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D000069059:Atorvastatin