Lu Fu1, Fang Rao1, Feihong Lian1, Hui Yang1, Sujuan Kuang1, Shulin Wu1, Chunyu Deng2, Yumei Xue3. 1. Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangzhou, 510080, China; Guangdong Provincial Key Laboratory of Clinical Pharmacology, Research Center of Medical Sciences, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China. 2. Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangzhou, 510080, China; Guangdong Provincial Key Laboratory of Clinical Pharmacology, Research Center of Medical Sciences, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China. Electronic address: chunyudeng@126.com. 3. Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangzhou, 510080, China; Guangdong Provincial Key Laboratory of Clinical Pharmacology, Research Center of Medical Sciences, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China. Electronic address: xymgdci@163.com.
Abstract
AIMS: To explore the atrial electrical remodeling and the susceptibility of atrial fibrillation (AF) in diabetic rats. MATERIALS AND METHODS: Zucker diabetic fatty (ZDF) rats were chosen as diabetic animal model, and age-matched non-diabetic littermate Zucker lean (ZL) rats as control. AF susceptibility was determined by electrophysiological examination. The current density of Ito, IKur and ICa-L were detected by whole-cell patch-clamp technique, and ion channel protein expression in atrial tissue and HL-1 cells treated with advanced glycation end products (AGE) was analyzed by western blotting. KEY FINDINGS: Diabetic rats had significantly enlarged left atria and evenly thickened ventricular walls, hypertrophied cells and interstitial fibrosis in atrial myocardium, increased AF susceptibility, and prolonged AF duration after atrial burst stimulation. Compared with atrial myocytes isolated from ZL controls, atrial myocytes isolated from ZDF rats had prolonged action potential duration, decreased absolute value of resting membrane potential level and current densities of Ito, IKur and ICa-L. The ion channel protein (Kv4.3, Kv1.5 and Cav1.2) expression in atrium tissue of ZDF rats and HL-1 cells treated with high concentration AGE were significantly down-regulated, compared with controls. SIGNIFICANCE: The atrial electrical remodeling induced by hyperglycemia contributed to the increased AF susceptibility in diabetic rats.
AIMS: To explore the atrial electrical remodeling and the susceptibility of atrial fibrillation (AF) in diabeticrats. MATERIALS AND METHODS:Zucker diabetic fatty (ZDF) rats were chosen as diabetic animal model, and age-matched non-diabetic littermate Zucker lean (ZL) rats as control. AF susceptibility was determined by electrophysiological examination. The current density of Ito, IKur and ICa-L were detected by whole-cell patch-clamp technique, and ion channel protein expression in atrial tissue and HL-1 cells treated with advanced glycation end products (AGE) was analyzed by western blotting. KEY FINDINGS:Diabeticrats had significantly enlarged left atria and evenly thickened ventricular walls, hypertrophied cells and interstitial fibrosis in atrial myocardium, increased AF susceptibility, and prolonged AF duration after atrial burst stimulation. Compared with atrial myocytes isolated from ZL controls, atrial myocytes isolated from ZDFrats had prolonged action potential duration, decreased absolute value of resting membrane potential level and current densities of Ito, IKur and ICa-L. The ion channel protein (Kv4.3, Kv1.5 and Cav1.2) expression in atrium tissue of ZDFrats and HL-1 cells treated with high concentration AGE were significantly down-regulated, compared with controls. SIGNIFICANCE: The atrial electrical remodeling induced by hyperglycemia contributed to the increased AF susceptibility in diabeticrats.
Authors: Martin Aguilar; Robert A Rose; Abhijit Takawale; Stanley Nattel; Svetlana Reilly Journal: Cardiovasc Res Date: 2021-06-16 Impact factor: 10.787