Exosomes in atrial fibrillation: therapeutic potential and role as clinical biomarkers

Author(s):  
Kun Xiang ◽  
Muhammad Akram ◽  
Walaa Fikry Elbossaty ◽  
Jinfu Yang ◽  
Chengming Fan
2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Meng Li ◽  
Junping Zhang

MicroRNAs (miRNAs) are composed of a group of endogenous and noncoding small RNAs which control expression of complementary target mRNAs. The extended functions of miRNAs enhance the complexity of gene-regulatory processes in cardiovascular and cerebrovascular diseases. Indeed, recent studies have shown that miRNAs are closely related to myocardial infarction, heart failure, atrial fibrillation, cardiomyopathy, hypertension, angiogenesis, coronary artery disease, dyslipidaemia, stroke, and so forth. These findings suggest a new therapeutic pointcut for cardiovascular and cerebrovascular diseases and show the extensive therapeutic potential of miRNA regulation. Moreover, it has been shown that circulating extracellular miRNAs are stable in bodily fluids, which indicates circulating miRNAs as potential and emerging biomarkers for noninvasive diagnosis. This review highlights the most recent findings indicative of circulating miRNAs as potential clinical biomarkers for diagnosis of cardiovascular and cerebrovascular diseases.


2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Mariana Floria ◽  
Smaranda Radu ◽  
Evelina Maria Gosav ◽  
Aurelian Corneliu Moraru ◽  
Teodor Serban ◽  
...  

Although rarely life-threatening on short term, atrial fibrillation leads to increased mortality and decreased quality of life through its complications, including heart failure and stroke. Recent studies highlight the benefits of maintaining sinus rhythm. However, pharmacological long-term rhythm control strategies may be shadowed by associated proarrhythmic effects. At the same time, electrical cardioversion is limited to hospitals, while catheter ablation therapy, although effective, is invasive and is dedicated to specific patients, usually with low amounts of atrial fibrosis (preferably Utah I-II). Cardiac optogenetics allows influencing the heart’s electrical activity by applying specific wavelength light pulses to previously engineered cardiomyocytes into expressing microbial derived light-sensitive proteins called opsins. The resulting ion influx may give rise to either hyperpolarizing or depolarizing currents, thus offering a therapeutic potential in cardiac electrophysiology, including pacing, resynchronization, and arrhythmia termination. Optogenetic atrial fibrillation cardioversion might be achieved by inducing a conduction block or filling of the excitable gap. The authors agree that transmural opsin expression and appropriate illumination with an exposure time longer than the arrhythmia cycle length are necessary to achieve successful arrhythmia termination. However, the efficiency and safety of biological cardioversion in humans remain to be seen, as well as side effects such as immune reactions and loss of opsin expression. The possibility of delivering pain-free shocks with out-of-hospital biological cardioversion is tempting; however, there are several issues that need to be addressed first: applicability and safety in humans, long-term behaviour, anticoagulation requirements, and fibrosis interactions.


2021 ◽  
Author(s):  
Aneesh Bapat ◽  
Guoping Li ◽  
Ling Xiao ◽  
Maarten Hulsmans ◽  
Maximilian J Schloss ◽  
...  

Rationale: Given its rising prevalence in both the adult and pediatric populations, obesity has become an increasingly important risk factor in the development of atrial fibrillation. However, a better mechanistic understanding of obesity-related atrial fibrillation is required. Serum glucocorticoid kinase 1 (SGK1) is a kinase positioned downstream of multiple obesity-related pathways, and prior work has shown a pathologic role for SGK1 signaling in ventricular remodeling and arrhythmias. Objective: To determine the mechanistic basis of obesity associated atrial fibrillation and explore the therapeutic potential of targeting SGK1 in this context. Methods and Results: We utilized a mouse model of diet induced obesity to determine the atrial electrophysiologic effects of obesity using electrophysiologic studies, optical mapping, and biochemical analyses. In C57BL/6J mice fed a high fat diet, there was upregulation of SGK1 signaling along with an increase in AF inducibility determined at electrophysiology (EP) study. These changes were associated with an increase in fibrotic and inflammatory signaling. Transgenic mice expressing a cardiac specific dominant negative SGK1 (SGK1 DN) were protected from obesity-related AF as well as the fibrotic and inflammatory consequences of AF. Finally, optical mapping demonstrated a shorter action potential duration and patch clamp revealed effects on INa, with a decreased peak current as well as a depolarizing shift in activation/inactivation properties in atrial myocytes. Conclusions: Diet induced obesity leads to increased cardiac SGK1 signaling as well as an increase in AF inducibility in obese mice. Genetic SGK1 inhibition reduced AF inducibility, and this effect may be mediated by effects on inflammation, fibrosis, and cellular electrophysiology. 


2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Xiaona Xu ◽  
Zhiqiang Zhao ◽  
Guangping Li

One of the most globally prevalent supraventricular arrhythmias is atrial fibrillation (AF). Knowledge of the structures and functions of messenger RNA (mRNA) has recently increased. It is no longer viewed as solely an intermediate molecule between DNA and proteins but has come to be seen as a dynamic and modifiable gene regulator. This new perspective on mRNA has led to rising interest in it and its presence in research into new therapeutic schemes. This paper, therefore, focuses on microRNAs (miRNAs), which are small noncoding RNAs that regulate posttranscriptional gene expression and play a vital role in the physiology and normative development of cardiovascular systems. This means they play an equally vital role in the development and progression of cardiovascular diseases. In recent years, multiple studies have pinpointed particular miRNA expression profiles as being associated with varying histological features of AF. These studies have been carried out in both animal models and AF patients. The emergence of miRNAs as biomarkers and their therapeutic potential in AF patients will be discussed in the body of this paper.


2021 ◽  
Vol 22 (1) ◽  
pp. 442
Author(s):  
Stan W. van Wijk ◽  
Kennedy S. Ramos ◽  
Bianca J. J. M. Brundel

Atrial fibrillation (AF) is the most common age-related cardiac arrhythmia worldwide and is associated with ischemic stroke, heart failure, and substantial morbidity and mortality. Unfortunately, current AF therapy is only moderately effective and does not prevent AF progression from recurrent intermittent episodes (paroxysmal) to persistent and finally permanent AF. It has been recognized that AF persistence is related to the presence of electropathology. Electropathology is defined as structural damage, including degradation of sarcomere structures, in the atrial tissue which, in turn, impairs electrical conduction and subsequently the contractile function of atrial cardiomyocytes. Recent research findings indicate that derailed proteostasis underlies structural damage and, consequently, electrical conduction impairment. A healthy proteostasis is of vital importance for proper function of cells, including cardiomyocytes. Cells respond to a loss of proteostatic control by inducing a heat shock response (HSR), which results in heat shock protein (HSP) expression. Emerging clinical evidence indicates that AF-induced proteostasis derailment is rooted in exhaustion of HSPs. Cardiomyocytes lose defense against structural damage-inducing pathways, which drives progression of AF and induction of HSP expression. In particular, small HSPB1 conserves sarcomere structures by preventing their degradation by proteases, and overexpression of HSPB1 accelerates recovery from structural damage in experimental AF model systems. In this review, we provide an overview of the mechanisms of action of HSPs in preventing AF and discuss the therapeutic potential of HSP-inducing compounds in clinical AF, as well as the potential of HSPs as biomarkers to discriminate between the various stages of AF and recurrence of AF after treatment.


Sign in / Sign up

Export Citation Format

Share Document