Abstract
BackgroundStructural remodeling is critical to the initiation and maintenance of atrial fibrillation (AF). IGF1, insulin like growth factor 1, has been recognized as contributor to fibrosis. However, the roles and mechanisms of IGF1 in structural remodeling during AF is still unclear.MethodsWe investigated the transcriptional expression profiles of left atria in AF and non-AF rat models by using microarray analysis. And quantitative real-time polymerase chain reaction (qRT-PCR) was performed to validate the accuracy. After bioinformatics analysis, IGF1 was selected to explore its effects and mechanisms on atrial fibrosis. The fibroblasts were extracted from atria of rats, and randomly divided into negative control group, mIGF1 overexpression group and mIGF1 silencing group. Then 30 healthy male Wistar rats were randomly divided into negative control group (n = 10), pacing group (n = 10), pacing + mIGF1 silencing viruses group (n = 10). Then the intracardiac electrophysiological examination, qRT-PCR, Western Blotting, masson staining were conducted after IGF1 interfering experiments.ResultsA total of 956 differentially expressed transcripts were identified, in which 395 transcripts were down-regulated and 561 transcripts were up-regulated. Bioinformatics analysis was conducted to predict the functions and interactions of the aberrantly expressed genes. The inhibition of IGF1 function in AF model could ameliorate the inducibility of AF. The IGF1 plays a fibrotic role by activating the PI3K-Akt pathway to increase the expression of CTGF and AT1R.ConclusionsIGF1 develops vital function in regulating structural remodeling during AF, which could illustrate the mechanism of AF pathogenesis and supply potential targets for its precise treatment.
Highlights
Structural remodeling is critical to the initiation and maintenance of atrial fibrillation (AF)
We identified that AF was induced successfully if the irregular frequent atrial rhythms sustaining > 10 s, and the irregular frequent atrial rhythms lasting < 10 s was considered as paroxysmal atrial tachycardia (PAT)
PAT occurred in all 10 rats in AF group, while PAT existed in 3 rats in control group (Fig. 1c)
Summary
Structural remodeling is critical to the initiation and maintenance of atrial fibrillation (AF). The roles and mechanisms of IGF1 in structural remodeling during AF is still unclear. Atrial fibrillation (AF) is a disorder of atrial electrical activity, which is one of the most common rapid arrhythmias. Many progress has been made in the treatment of AF, the therapeutic effect of AF is still not satisfactory, which is closely related to its unclear mechanism. Structural remodeling, electrical remodeling, autonomic nerve remodeling and energy. The aim of this study is to explore the expression profile of mRNAs transcriptome after atrial remodeling during AF and determine the key molecular that play significant roles in atrial remodeling during AF, in order to illustrate the new molecular mechanism for atrial remodeling during AF and provide potential targets for optimizing the treatment of AF
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