Intracellular lactate signaling cascade in atrial remodeling of mitral valvular patients with atrial fibrillation

Jing Xu,Shijiang Zhang,Xiaohan Xu,Lei Xue,Jianwei Qin,Xiaowei Wang,Yijiang Chen,Yongfeng Shao,Linjie Si,Yanhu Wu

doi:10.1186/1749-8090-8-34

Abstract

BackgroundAtrial remodeling has emerged as the structural basis for the maintenance and recurrence of atrial fibrillation. Lactate signaling cascade was recently linked to some cardiovascular disorders for its regulatory functions to myocardial structural remodeling. It was hypothesized that lactate signaling cascade was involved in the maintenance and recurrence of atrial fibrillation by regulating atrial structural remodeling.MethodsBiopsies of right atrial appendage and clinical data were collected from sex- and age-matched 30 persistent atrial fibrillation, 30 paroxysmal atrial fibrillation, 30 sinus rhythm patients undergoing isolated mitral valve surgery and 10 healthy heart donors.ResultsAtrial fibrillation groups had higher atrial lactate expression and this upregulated expression was positively correlated with regulatory indicators of atrial structural remodeling as reflected by severe oxidative stress injury and mitochondrial control of apoptosis.ConclusionsThe present findings suggest a potential role for lactate signaling cascade in the maintenance and recurrence of atrial fibrillation and possibly represent new targets for therapeutic intervention in this disorder.

Highlights

Atrial remodeling has emerged as the structural basis for the maintenance and recurrence of atrial fibrillation
The fundamental mechanism underlying Atrial fibrillation (AF) is primarily characterized by electrical remodeling, but limited success rates and uncertain long-term outcomes of current therapies based on this hypothesis, indicate that apart from electrical remodeling other factors are involved in development of AF [5]
The history of valvular disease was longer in Persistent AF (PeAF) than that of sinus rhythm (SR) and Paroxysmal AF (PaAF)

Summary

Introduction

Atrial remodeling has emerged as the structural basis for the maintenance and recurrence of atrial fibrillation. It was hypothesized that lactate signaling cascade was involved in the maintenance and recurrence of atrial fibrillation by regulating atrial structural remodeling. The notion of “upstream therapy”, targeting the processes involved in the development of the substrate of AF, has increasingly become the focus of attempts at therapeutic innovation. The fundamental mechanism underlying AF is primarily characterized by electrical remodeling, but limited success rates and uncertain long-term outcomes of current therapies based on this hypothesis, indicate that apart from electrical remodeling other factors are involved in development of AF [5]. In the recent decade, increasing experimental studies and clinical investigations have demonstrated that, in addition to electrical remodeling, atrial structural remodeling, especially inflammation, interstitial fibrosis, myocardial apoptosis and oxidative stress, occurs in maintenance and recurrence of AF, creating more favorable substrates for AF [6]. Targeting the regulation of atrial structural remodeling may be a promising therapeutic direction

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Results

Discussion

Conclusion