Lilei Yu1, Guannan Meng1, Bing Huang1, Xiaoya Zhou1, Stavros Stavrakis2, Menglong Wang1, Xuefei Li1, Liping Zhou1, Yuhong Wang1, Meng Wang1, Zhenya Wang1, Jielin Deng1, Sunny S Po3, Hong Jiang4. 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. Heart Rhythm Institute and Section of Cardiovascular Diseases, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. 3. Heart Rhythm Institute and Section of Cardiovascular Diseases, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. Electronic address: sunny-po@ouhsc.edu. 4. 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: hong-jiang@whu.edu.cn.
Abstract
BACKGROUND: Emerging evidence indicates gut microbes and their products could activate the autonomic nervous system (ANS), which plays important roles in the initiation and maintenance of atrial fibrillation (AF). Trimethylamine N-oxide (TMAO), a metabolite derived from gut microbes, is associated with cardiovascular diseases. The present study aimed to investigate the role of TMAO in the progression of AF. METHODS: In part 1: TMAO or saline was locally injected into 4 major atrial ganglionated plexi (GP) to clarify its effect on cardiac ANS and AF inducibility in normal canines. In part 2: TMAO or saline was injected into 4 major atrial GP to test its effect on AF progression in a rapid atrial pacing (RAP)-induced AF model. RESULTS: In part 1: Local injection of TMAO significantly increased anterior right GP (ARGP) function and neural activity, shortened ERP values. In part 2, compared with the control group, 6-hour RAP significantly shortened the ERP, widened the ∑WOV, enhanced the ARGP function and neural activity, increased the NGF and c-fos expression, and up-regulated the inflammatory cytokines. TMAO aggravated all of these changes by activating the proinflammatory p65 NF-κB signaling pathway. CONCLUSIONS: TMAO could increase the instability of atrial electrophysiology in normal canines and aggravate the acute electrical remodeling in a RAP-induced AF model by exacerbating autonomic remodeling. The increased inflammatory cytokines in the GP due to the activation of p65 NF-κB signaling may contribute to these effects.
BACKGROUND: Emerging evidence indicates gut microbes and their products could activate the autonomic nervous system (ANS), which plays important roles in the initiation and maintenance of atrial fibrillation (AF). Trimethylamine N-oxide (TMAO), a metabolite derived from gut microbes, is associated with cardiovascular diseases. The present study aimed to investigate the role of TMAO in the progression of AF. METHODS: In part 1: TMAO or saline was locally injected into 4 major atrial ganglionated plexi (GP) to clarify its effect on cardiac ANS and AF inducibility in normal canines. In part 2: TMAO or saline was injected into 4 major atrial GP to test its effect on AF progression in a rapid atrial pacing (RAP)-induced AF model. RESULTS: In part 1: Local injection of TMAO significantly increased anterior right GP (ARGP) function and neural activity, shortened ERP values. In part 2, compared with the control group, 6-hour RAP significantly shortened the ERP, widened the ∑WOV, enhanced the ARGP function and neural activity, increased the NGF and c-fos expression, and up-regulated the inflammatory cytokines. TMAO aggravated all of these changes by activating the proinflammatory p65 NF-κB signaling pathway. CONCLUSIONS:TMAO could increase the instability of atrial electrophysiology in normal canines and aggravate the acute electrical remodeling in a RAP-induced AF model by exacerbating autonomic remodeling. The increased inflammatory cytokines in the GP due to the activation of p65 NF-κB signaling may contribute to these effects.
Authors: Monika Gawałko; Thomas A Agbaedeng; Arnela Saljic; Dominik N Müller; Nicola Wilck; Renate Schnabel; John Penders; Michiel Rienstra; Isabelle van Gelder; Thomas Jespersen; Ulrich Schotten; Harry J G M Crijns; Jonathan M Kalman; Prashanthan Sanders; Stanley Nattel; Dobromir Dobrev; Dominik Linz Journal: Cardiovasc Res Date: 2022-08-24 Impact factor: 13.081
Authors: B O Nguyen; L M G Meems; M van Faassen; H J G M Crijns; I C van Gelder; F Kuipers; M Rienstra Journal: Int J Cardiol Heart Vasc Date: 2021-05-24