Cardioprotective Role of Heat Shock Proteins in Atrial Fibrillation: From Mechanism of Action to Therapeutic and Diagnostic Target

Wijk, Stan W. van; Ramos, Kennedy Silva; Brundel, Bianca J. J. M.

doi:10.3390/ijms22010442

Cited by 11 publications

(7 citation statements)

References 87 publications

(48 reference statements)

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“…ZFP36 has been linked to a variety of autoimmune diseases such as rheumatoid arthritis, psoriasis, multiple sclerosis, and juvenile idiopathic arthritis ( 39 ). The P2X7 receptor (P2RX7) is mainly expressed in immune cells and serves as an essential regulator of inflammation, immunity, and cellular death ( 21 , 40 ). P2RX7 is associated with several cardiovascular diseases, including hypertension, atherosclerosis, ischemia/reperfusion injury, and heart failure ( 21 ).…”

Section: Discussionmentioning

confidence: 99%

“…The P2X7 receptor (P2RX7) is mainly expressed in immune cells and serves as an essential regulator of inflammation, immunity, and cellular death ( 21 , 40 ). P2RX7 is associated with several cardiovascular diseases, including hypertension, atherosclerosis, ischemia/reperfusion injury, and heart failure ( 21 ). This is due to its role in promoting endothelial dysfunction and inflammation.…”

Section: Discussionmentioning

confidence: 99%

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Genome-wide analysis of RNA-binding proteins co-expression with alternative splicing events in mitral valve prolapse

et al. 2023

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ObjectivesWe investigated the role and molecular mechanisms of RNA-binding proteins (RBPs) and their regulated alternative splicing events (RASEs) in the pathogenesis of mitral valve prolapse (MVP). MethodsFor RNA extraction, we obtained peripheral blood mononuclear cells (PBMCs) from five patients with MVP, with or without chordae tendineae rupture, and five healthy individuals. High-throughput sequencing was used for RNA sequencing (RNA-seq). Differentially expressed genes (DEGs) analysis, alternative splicing (AS) analysis, functional enrichment analysis, co-expression of RBPs, and alternative splicing events (ASEs) analysis were conducted.ResultsThe MVP patients exhibited 306 up-regulated genes and 198 down-regulated genes. All down- and up-regulated genes were enriched in both Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Furthermore, MVP was closely associated with the top 10 enriched terms and pathways. In MVP patients, 2,288 RASEs were found to be significantly different, and four suitable RASEs (CARD11 A3ss, RBM5 ES, NCF1 A5SS, and DAXX A3ss) were tested. We identified 13 RNA-binding proteins (RBPs) from the DEGs and screened out four RBPs (ZFP36, HSPA1A, TRIM21, and P2RX7). We selected four RASEs based on the co-expression analyses of RBPs and RASEs, including exon skipping (ES) of DEDD2, alternative 3′ splice site (A3SS) of ETV6, mutually exclusive 3′UTRs (3pMXE) of TNFAIP8L2, and A3SS of HLA-B. Furthermore, the selected four RBPs and four RASEs were validated by reverse transcription–quantitative polymerase chain reaction (RT-qPCR) and showed high consistency with RNA sequencing (RNA-seq).ConclusionDysregulated RBPs and their associated RASEs may play regulatory roles in MVP development and may therefore be used as therapeutic targets in the future.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Genome-wide analysis of RNA-binding proteins co-expression with alternative splicing events in mitral valve prolapse

et al. 2023

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“…To change the current poor situation of AF management, increasing attention is dedicated to the dissection of the molecular and electrical mechanisms of AF occurrence. Currently, electropathology, which is defined as the impairment of electrical activation (electrical and calcium remodeling) caused by molecular defects in cardiomyocytes that lead to structural damage (cardiac remodeling), is considered to play a critical role in driving AF ( 22 , 23 ). Moreover, abnormal autonomic innervation (autonomic nerve remodeling) is involved in electropathology, causing markedly heterogeneous changes in atrial electrophysiology and inducing atrial tachyarrhythmia ( 24 ).…”

Section: Discussionmentioning

confidence: 99%

Angiotensin receptor-neprilysin inhibitor therapy and recurrence of atrial fibrillation after radiofrequency catheter ablation: A propensity-matched cohort study

Dong

Xiao

et al. 2022

Front. Cardiovasc. Med.

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BackgroundCompared with conventional medicines, angiotensin receptor-neprilysin inhibitor (ARNI) could further improve the prognosis for multiple cardiovascular diseases, such as heart failure, hypertension, and myocardial infarction. However, the relationship between ARNI therapy and the recurrence of atrial fibrillation (AF) after radiofrequency catheter ablation is currently unknown.MethodsThis study is a retrospective cohort study. Patients with consecutive persistent or paroxysmal AF undergoing first-time radiofrequency ablation were enrolled from February 2018 to October 2021. We compared the risk of AF recurrence in patients with catheter ablation who received ARNI with the risk of AF recurrence in those who received the angiotensin-converting enzyme inhibitor (ACEI). The propensity-score matched analysis was conducted to examine the effectiveness of ARNI. We used a Cox regression model to evaluate AF recurrence events.ResultsAmong 679 eligible patients, 155 patients with ARNI treatment and 155 patients with ACEI treatment were included in the analyses. At a median follow-up of 228 (196–322) days, ARNI as compared with ACEI was associated with a lower risk of AF recurrence [adjusted hazard ratio (HR), 0.39; 95% confidence interval (CI), 0.24–0.63; p < 0.001]. In addition, no interaction was found in the subgroup analysis.ConclusionAngiotensin receptor-neprilysin inhibitor treatment was associated with a decreased risk of AF recurrence after first-time radiofrequency catheter ablation.

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“…Currently, there has been increasing interest in nuclear-encoded mitochondrial HSPs as a potential serum biomarker in AF [102]. Interestingly, HSPs have been shown to halt or even reverse structural damage in experimental AF model systems [103].…”

Section: Mitochondrial Heat Shock Proteins In Afmentioning

confidence: 99%

The Role of Mitochondrial Dysfunction in Atrial Fibrillation: Translation to Druggable Target and Biomarker Discovery

Pool

Wijdeveld

Groot

et al. 2021

IJMS

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Atrial fibrillation (AF) is the most prevalent and progressive cardiac arrhythmia worldwide and is associated with serious complications such as heart failure and ischemic stroke. Current treatment modalities attenuate AF symptoms and are only moderately effective in halting the arrhythmia. Therefore, there is an urgent need to dissect molecular mechanisms that drive AF. As AF is characterized by a rapid atrial activation rate, which requires a high energy metabolism, a role of mitochondrial dysfunction in AF pathophysiology is plausible. It is well known that mitochondria play a central role in cardiomyocyte function, as they produce energy to support the mechanical and electrical function of the heart. Details on the molecular mechanisms underlying mitochondrial dysfunction are increasingly being uncovered as a contributing factor in the loss of cardiomyocyte function and AF. Considering the high prevalence of AF, investigating the role of mitochondrial impairment in AF may guide the path towards new therapeutic and diagnostic targets. In this review, the latest evidence on the role of mitochondria dysfunction in AF is presented. We highlight the key modulators of mitochondrial dysfunction that drive AF and discuss whether they represent potential targets for therapeutic interventions and diagnostics in clinical AF.

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Cardioprotective Role of Heat Shock Proteins in Atrial Fibrillation: From Mechanism of Action to Therapeutic and Diagnostic Target

Cited by 11 publications

References 87 publications

Genome-wide analysis of RNA-binding proteins co-expression with alternative splicing events in mitral valve prolapse

Genome-wide analysis of RNA-binding proteins co-expression with alternative splicing events in mitral valve prolapse

Angiotensin receptor-neprilysin inhibitor therapy and recurrence of atrial fibrillation after radiofrequency catheter ablation: A propensity-matched cohort study

The Role of Mitochondrial Dysfunction in Atrial Fibrillation: Translation to Druggable Target and Biomarker Discovery

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