Lilei Yu1, Yuhong Wang1, Xiaoya Zhou1, Bing Huang1, Menglong Wang1, Xuefei Li1, Guannan Meng1, Shenxu Yuan1, Hao Xia2, Hong Jiang3. 1. Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China; Cardiovascular Research Institute, Wuhan University, Wuhan, Hubei, China; Hubei Key Laboratory of Cardiology, Wuhan, Hubei, China. 2. Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China; Cardiovascular Research Institute, Wuhan University, Wuhan, Hubei, China; Hubei Key Laboratory of Cardiology, Wuhan, Hubei, China. Electronic address: xiahao1966@163.com. 3. Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China; Cardiovascular Research Institute, Wuhan University, Wuhan, Hubei, China; Hubei Key Laboratory of Cardiology, Wuhan, Hubei, China. Electronic address: whujianghong@163.com.
Abstract
BACKGROUND: Leptin is a peptide hormone produced by adipose tissue whose basic function is regulating energy balance and sympathetic outflow. Previous studies have shown that increased nerve activity of the left stellate ganglion (LSG) promotes ventricular arrhythmia (VA). OBJECTIVE: The purpose of this study was to investigate whether leptin could facilitate VA through activation of the LSG. METHODS: Sixteen pentobarbital-anesthetized dogs were divided into a control group (saline; n = 8) and a leptin group (leptin; n = 8). Microinjections of either 0.1 mL saline or leptin (18 μg) were injected into the LSG. Action potential duration (APD) of the myocyte and the function and neural activity of the LSG were measured at different time points. VA induced by occlusion of the left anterior descending branch was continuously measured for 1 hour. At the end of the experiment, the LSG tissues were collected for molecular detections. RESULTS: Compared with the control group, leptin microinjection resulted in (1) significant enhancement in the incidence of VA; (2) significant decrease in APD and increase in APD dispersion; and (3) significant increase in the function and neural activity of the LSG. Mechanistically, the leptin receptor was found in the LSG, and its signaling was significantly activated in the leptin-injected group. Additionally, leptin microinjection markedly increased the expression of proinflammatory cytokines. CONCLUSION: LSG activation induced by leptin microinjection promotes ischemia-induced VAs. Activated leptin receptor signaling and up-regulation of proinflammatory cytokines in the LSG may be responsible for these effects.
BACKGROUND:Leptin is a peptide hormone produced by adipose tissue whose basic function is regulating energy balance and sympathetic outflow. Previous studies have shown that increased nerve activity of the left stellate ganglion (LSG) promotes ventricular arrhythmia (VA). OBJECTIVE: The purpose of this study was to investigate whether leptin could facilitate VA through activation of the LSG. METHODS: Sixteen pentobarbital-anesthetized dogs were divided into a control group (saline; n = 8) and a leptin group (leptin; n = 8). Microinjections of either 0.1 mL saline or leptin (18 μg) were injected into the LSG. Action potential duration (APD) of the myocyte and the function and neural activity of the LSG were measured at different time points. VA induced by occlusion of the left anterior descending branch was continuously measured for 1 hour. At the end of the experiment, the LSG tissues were collected for molecular detections. RESULTS: Compared with the control group, leptin microinjection resulted in (1) significant enhancement in the incidence of VA; (2) significant decrease in APD and increase in APD dispersion; and (3) significant increase in the function and neural activity of the LSG. Mechanistically, the leptin receptor was found in the LSG, and its signaling was significantly activated in the leptin-injected group. Additionally, leptin microinjection markedly increased the expression of proinflammatory cytokines. CONCLUSION: LSG activation induced by leptin microinjection promotes ischemia-induced VAs. Activated leptin receptor signaling and up-regulation of proinflammatory cytokines in the LSG may be responsible for these effects.
Authors: João A B Pedroso; Ivson B da Silva; Thais T Zampieri; Leonardo T Totola; Thiago S Moreira; Ana P T Taniguti; Gabriela P Diniz; Maria Luiza M Barreto-Chaves; Jose Donato Journal: Int J Mol Sci Date: 2022-06-10 Impact factor: 6.208