Introduction
Atrial fibrillation (AF) is a common arrhythmia in clinical practice
[1]. A survey by Zhang Shu et al. [2] on 19,368 natural patients
aged 35 years old in different regions of China showed that the
age-adjusted prevalence of AF was approximately 0.74%. Globally, the
current prevalence of AF in adults is estimated to be between 2% and
4%, and is expected to increase [3-6]. AF represents a significant
burden to patients, doctors, and the healthcare system. AF is an
important cause of heart failure, ischemic stroke and other diseases,
which seriously harm the health of humans. With the continued updating
of diagnosis and treatment methods, the success rate of AF treatment is
gradually improving, but it still does not reach the expected goal.
Currently, the treatment of AF mainly includes drug control of
ventricular rate, drug cardioversion and maintenance sinus rhythm,
percutaneous radiofrequency catheter ablation, percutaneous cryoballoon
ablation, and surgical Mazes. However, drug therapy has disadvantages of
a low success rate and many side effects, while surgical Maze procedures
cause significant trauma and carry a high risk of perioperative death.
Ablation is more effective than drugs [7-10] and has been
recommended for AF in domestic and foreign guidelines [11, 12].
However, the long-term success rate of ablation for paroxysmal AF that
has been followed up over 1 year is only 50%–80% [13-15], and is
even lower for persistent AF [16]. Moreover, the degree of atrial
fibrosis is more severe in patients with persistent AF than in patients
with paroxymoron AF. Atrial fibrosis is closely related to the
occurrence and maintenance of AF. Treatment of atrial fibrosis can
effectively reduce the occurrence and burden of AF, but the current
clinical methods are limited and ineffective. Therefore, it is important
to further study the mechanism of atrial fibrosis and its relationship
with the occurrence and development of AF.
Bromodomain-containing protein 4 (BRD4) plays an important role in the
process of fibrosis by regulating cell transcription and the cell cycle.
Recent studies have found that BRD4 inhibitors can be used for treating
fibrotic diseases via target gene-related pathways including the
extracellular matrix (ECM) receptor interaction, adhesion protein, PDGF
pathway, JNK/MAPK pathway, and the NF-κB pathway. Therefore, BRD4 is
considered a potential target in fibrosis. Studies have shown that the
inhibition of BRD4 expression can reduce myocardial cell apoptosis and
ventricular myocyte fibrosis [17-19]. In 2019, at the 40th Annual
Meeting of the American Heart Association, a wall report study presented
by Professor Yigang Li [20] found that BRD4 inhibition could reduce
the induction rate of AF and alleviate atrial fibrosis, suggesting that
BRD4 is a new target for treating atrial fibrosis and AF. This study was
the first to establish a link between BRD4 and atrial fibrosis and AF.
However, the correlation between the transforming growth factor-β
(TGF-β)/SMAD signaling pathway, which is closely related to AF and
atrial fibrosis, with BRD4 has not yet been reported. Furthermore, there
has been no clinical study on the expression of BRD4 in patients with AF
in combination with non-valvular disease and non-ischemic
cardiomyopathy. Additionally, the relationship between BRD4 and AF
recurrence after ablation remains unknown.
Based on the above views, we further verified the association between
BRD4 and AF and atrial fibrosis through clinical observation and animal
experiments. As the pathogenesis of AF in valvular disease is more
complex, the atrial fibrosis of nonvalvular atrial fibrillation (NVAF)
is most commonly caused by valvular disease itself, and valve
replacement is the basic treatment strategy. Valvular AF accounts for
approximately 12.9% of patients with AF, and the subjects of the
current study have NVAF.