scholarly journals Molecular mechanism of atrial remodeling in patients with aging atrial fibrillation under the expression of microRNA-1 and microRNA-21

Bioengineered ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 12905-12916
Author(s):  
Kexin Yuan ◽  
Pei Zhao ◽  
Lili Wang
2019 ◽  
Vol 26 (5) ◽  
pp. 888-897 ◽  
Author(s):  
Costas Tsioufis ◽  
Dimitris Konstantinidis ◽  
Ilias Nikolakopoulos ◽  
Evi Vemmou ◽  
Theodoros Kalos ◽  
...  

Background: Atrial fibrillation (AF) is the most frequently encountered cardiac arrhythmia globally and substantially increases the risk for thromboembolic disease. Albeit, 20% of all cases of AF remain undiagnosed. On the other hand, hypertension amplifies the risk for both AF occurrences through hemodynamic and non-hemodynamic mechanisms and cerebrovascular ischemia. Under this prism, prompt diagnosis of undetected AF in hypertensive patients is of pivotal importance. Method: We conducted a review of the literature for studies with biomarkers that could be used in AF diagnosis as well as in predicting the transition of paroxysmal AF to sustained AF, especially in hypertensive patients. Results: Potential biomarkers for AF can be broadly categorized into electrophysiological, morphological and molecular markers that reflect the underlying mechanisms of adverse atrial remodeling. We focused on P-wave duration and dispersion as electrophysiological markers, and left atrial (LA) and LA appendage size, atrial fibrosis, left ventricular hypertrophy and aortic stiffness as structural biomarkers, respectively. The heterogeneous group of molecular biomarkers of AF encompasses products of the neurohormonal cascade, including NT-pro BNP, BNP, MR-pro ANP, polymorphisms of the ACE and convertases such as corin and furin. In addition, soluble biomarkers of inflammation (i.e. CRP, IL-6) and fibrosis (i.e. TGF-1 and matrix metalloproteinases) were assessed for predicting AF. Conclusion: The reviewed individual biomarkers might be a valuable addition to current diagnostic tools but the ideal candidate is expected to combine multiple indices of atrial remodeling in order to effectively detect both AF and adverse characteristics of high risk patients with hypertension.


2015 ◽  
Vol 308 (2) ◽  
pp. H126-H134 ◽  
Author(s):  
Erin Harleton ◽  
Alessandra Besana ◽  
Parag Chandra ◽  
Peter Danilo ◽  
Tove S. Rosen ◽  
...  

Atrial fibrillation (AF) is a common arrhythmia with significant morbidities and only partially adequate therapeutic options. AF is associated with atrial remodeling processes, including changes in the expression and function of ion channels and signaling pathways. TWIK protein-related acid-sensitive K+ channel (TASK)-1, a two-pore domain K+ channel, has been shown to contribute to action potential repolarization as well as to the maintenance of resting membrane potential in isolated myocytes, and TASK-1 inhibition has been associated with the induction of perioperative AF. However, the role of TASK-1 in chronic AF is unknown. The present study investigated the function, expression, and phosphorylation of TASK-1 in chronic AF in atrial tissue from chronically paced canines and in human subjects. TASK-1 current was present in atrial myocytes isolated from human and canine hearts in normal sinus rhythm but was absent in myocytes from humans with AF and in canines after the induction of AF by chronic tachypacing. The addition of phosphatase to the patch pipette rescued TASK-1 current from myocytes isolated from AF hearts, indicating that the change in current is phosphorylation dependent. Western blot analysis showed that total TASK-1 protein levels either did not change or increased slightly in AF, despite the absence of current. In studies of perioperative AF, we have shown that phosphorylation of TASK-1 at Thr383 inhibits the channel. However, phosphorylation at this site was unchanged in atrial tissue from humans with AF or in canines with chronic pacing-induced AF. We conclude that phosphorylation-dependent inhibition of TASK-1 is associated with AF, but the phosphorylation site responsible for this inhibition remains to be identified.


Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Masayuki Shimano ◽  
Rei Shibata ◽  
Yukiomi Tsuji ◽  
Noriyuki Ouchi ◽  
Yasuya Inden ◽  
...  

The occurrence and development of atrial fibrillation (AF) are associated with changes in electrical properties and cardiac structure, known as electrical and structural atrial remodeling. AF characterized by atrial remodeling also occurs with obesity-related conditions. Adiponectin, an adipose tissue-derived hormone, exerts beneficial effects on the heart in various pathological conditions. These observations led us to speculate that adiponectin levels affect the development and prevalence of AF. Here, we investigated a potential association between circulating adiponectin levels and atrial remodeling in patients with AF. We measured plasma adiponectin levels, serum carboxy-terminal telopeptide of collagen type I (CITP) levels, as a collagen type I degradation marker, and serum type III procollagen-N-peptide (PIIINP) levels, as a collagen type III synthesis marker in consecutive 414 patients; 225 paroxysmal AF, 81 persistent AF and 108 paroxysmal supra-ventricular tachycardia without AF history (control) patients, who admitted for scheduled radiofrequency catheter ablation. Plasma adiponectin levels were significantly higher in patients with persistent AF compared to paroxysmal AF and control patients (p<0.05). Serum CITP levels, but not serum PIIINP levels, were also higher in patients with persistent AF compared to paroxysmal AF and control patients (p<0.05). In addition, a positive correlation was observed between adiponectin levels and CITP levels (r=0.39, p<0.005) or the P wave duration (r=−0.31, p<0.05) in patients with persistent AF. High plasma adiponectin levels are associated with the presence of persistent AF, which is accompanied by increased CITP levels. Hyperadiponectinemia might also attenuate atrial conduction disturbance. Thus, measurement of plasma adiponectin could be useful for assessment of AF.


Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Amir Schricker ◽  
Tina Baykaner ◽  
Junaid Zaman ◽  
Gautam Lalani ◽  
Kenneth Hopper ◽  
...  

Introduction: Targets for the ablation of atrial fibrillation (AF) are debated. In particular, recent studies questioning fractionated electrograms and lines has increased focus on AF substrates of rotors and focal impulses. These AF sources are seen in both atria, but have unknown etiology. We hypothesized that differential remodeling between the right atrium (RA), whose structural changes are largely undefined, and left atrium (LA) influence the distribution of AF sources and the outcomes from AF source ablation. Methods: In 60 patients at AF ablation (62±10 years, 60% persistent, 5% long-standing persistent), we compared size differences between RA and LA to the number of sources in each chamber and outcomes from AF source-guide ablation. We studied if a 64-pole basket differentially fit the LA or RA, judged by deformation of its splines by the atria (fig. A, B) over multiple cardiac cycles on fluoroscopy. Ablation targeted sources in both atria and was followed by PVI, with follow-up per guidelines. Results: Using baskets in both atria, 205 sources (LA 138; RA 67) were identified and ablated. Notably, the same basket in each patient was dynamically deformed by RA in 51 (85%) of cases but in the LA in only 39 (65%), indicating greater LA remodeling. The number of AF sources was higher in the presence of basket deformation of RA (n=174) than LA (n=130). LA deformation correlated with LVEF (p=0.05). Freedom from AF at 1 year was reduced in patients with no basket deformation (i.e. dilation) in LA (p=0.07) or RA (p=0.06). Notably, single procedure AF freedom was substantially lower in patients with differential remodeling (deformation in only 1 chamber) of 84% vs. 60% (fig C). Conclusions: Structural atrial remodeling influences the number of electrical rotors and focal sources in each chamber. A mismatch between right and left atrial remodeling predicts lower success from rotor ablation. These data also provide novel clinical indices of effective basket positioning.


2021 ◽  
Vol 7 ◽  
Author(s):  
Tao Yan ◽  
Shijie Zhu ◽  
Miao Zhu ◽  
Chunsheng Wang ◽  
Changfa Guo

Background: Atrial fibrillation (AF) is the most common tachyarrhythmia in the clinic, leading to high morbidity and mortality. Although many studies on AF have been conducted, the molecular mechanism of AF has not been fully elucidated. This study was designed to explore the molecular mechanism of AF using integrative bioinformatics analysis and provide new insights into the pathophysiology of AF.Methods: The GSE115574 dataset was downloaded, and Cibersort was applied to estimate the relative expression of 22 kinds of immune cells. Differentially expressed genes (DEGs) were identified through the limma package in R language. Weighted gene correlation network analysis (WGCNA) was performed to cluster DEGs into different modules and explore relationships between modules and immune cell types. Functional enrichment analysis was performed on DEGs in the significant module, and hub genes were identified based on the protein-protein interaction (PPI) network. Hub genes were then verified using quantitative real-time polymerase chain reaction (qRT-PCR).Results: A total of 2,350 DEGs were identified and clustered into eleven modules using WGCNA. The magenta module with 246 genes was identified as the key module associated with M1 macrophages with the highest correlation coefficient. Three hub genes (CTSS, CSF2RB, and NCF2) were identified. The results verified using three other datasets and qRT-PCR demonstrated that the expression levels of these three genes in patients with AF were significantly higher than those in patients with SR, which were consistent with the bioinformatic analysis.Conclusion: Three novel genes identified using comprehensive bioinformatics analysis may play crucial roles in the pathophysiological mechanism in AF, which provide potential therapeutic targets and new insights into the treatment and early detection of AF.


2020 ◽  
Vol 17 (4) ◽  
pp. 49-60
Author(s):  
Maria-Luiza Toplicianu-Dimitriu ◽  
Ioan Tiberiu Nanea

AbstractAtrial fibrillation (AF) is the most common cardiac arrhythmia, with an increasing prevalence and an enormous clinical impact due to the high stroke rate, left ventricular dysfunction and excess mortality. The occurrence and maintenance of AF is favored by both the degree of left atrial (LA) dilation and the association of fibrotic lesions of the myocardium. The LA is a marker of adverse cardiovascular events in patients with AF. Atrial remodeling can be electrical (shortening atrial refractory), structural (altering geometry and altering collagen content) and contractile (loss of contractility). Cardiac imaging plays a central role in the clinical management of this arrhythmia. Echocardiography represents the routine imaging technique used in patients with AF, with a role in detecting LA dysfunction and cardiac structural changes that predispose to this arrhythmia, also having the ability to predict the maintenance of sinus rhythm after cardioversion and after ablation.


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