Research Progress of Myocardial Fibrosis and Atrial Fibrillation

Abstract

With the aging population and the increasing incidence of basic illnesses such as hypertension and diabetes (DM), the incidence of atrial fibrillation (AF) has increased significantly. AF is the most common arrhythmia in clinical practice, which can cause heart failure (HF) and ischemic stroke (IS), increasing disability and mortality. Current studies point out that myocardial fibrosis (MF) is one of the most critical substrates for the occurrence and maintenance of AF. Although myocardial biopsy is the gold standard for evaluating MF, it is rarely used in clinical practice because it is an invasive procedure. In addition, serological indicators and imaging methods have also been used to evaluate MF. Nevertheless, the accuracy of serological markers in evaluating MF is controversial. This review focuses on the pathogenesis of MF, serological evaluation, imaging evaluation, and anti-fibrosis treatment to discuss the existing problems and provide new ideas for MF and AF evaluation and treatment.

Keywords: atrial fibrillation; collagen; extracellular matrix; fibroblasts; myocardial fibrosis.

FIGURE 1

TGF-beta binds to the Type II receptor and recruits the Type I receptor, whereby the Type II receptor phosphorylates and activates Type I. The Type I receptor, in turn, phosphorylates receptor-activated Smad2 and Smad3. Then Smad2, Smad3, and Smad4 combine and translocate into the nucleus together. The interaction of the Smad complex with other DNA binding proteins (transcription factors, coactivator proteins, co-repressor proteins) activates specific gene expression.

FIGURE 2

RAAS system activation leads to increased secretion of aldosterone, which stimulates macrophages to secrete increased amounts of Gal-3, and it acts as a ligand to bind to TLR-4, further activating downstream MyD88, NF-κB signaling pathway that facilitates the increase of inflammatory factor IL-1β, IL-18, α-TNF, and collagen I, collagen III, then leads to myocardial remodeling and fibrosis.