کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2929025 1576154 2015 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Pro-arrhythmic action of autoantibodies against the second extracellular loop of β1-adrenoceptor and its underlying molecular mechanisms
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی کاردیولوژی و پزشکی قلب و عروق
پیش نمایش صفحه اول مقاله
Pro-arrhythmic action of autoantibodies against the second extracellular loop of β1-adrenoceptor and its underlying molecular mechanisms
چکیده انگلیسی

ObjectivesThe incidence of arrhythmia is associated with autoantibodies against the second extracellular loop of β1-adrenergic receptor (β1-AAbs). The current study was designed to determine the mechanisms by which arrhythmia experimentally might be induced by β1-AAbs.MethodsBlood samples were collected from patients with varied arrhythmias or coronary heart disease (CHD) and healthy subjects. The titer of β1-AAbs was assessed. Passive immunization rat models with β1-AAbs were established to determine whether β1-AAbs induced arrhythmia. Conventional intracellular microelectrode technique and whole cell patch clamp were employed to record action potential duration (APD), resting potential (RP), L-type calcium current (ICa-L), sodium–calcium exchange current (INCX), transient outward potassium current (Ito), inward rectifier potassium current (Ik1) and delayed rectifier potassium current (Ik).ResultsHigh levels of β1-AAbs were found in the sera of heart disease patients, especially in ventricular arrhythmia (VA). Transfusion with β1-AAbs could induce arrhythmias in normal rats in vivo. β1-AAbs purified from the sera of active immunized rats induced triggered activity (TA), delayed after depolarization (DAD), and prolonged APD in the papillary muscles of rats. β1-AAbs prolonged QT interval, increased ICa-L and decreased IK1, Ito and INa–Ca in rat ventricular myocytes in vitro. All these effects can be inhibited by β1-AR blocker metoprolol.ConclusionsThese results demonstrate for the first time that β1-AAbs could directly induce ventricular arrhythmia by prolonging QT interval.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: International Journal of Cardiology - Volume 198, 1 November 2015, Pages 251–258
نویسندگان
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