scholarly journals Myocardial fibrosis and atrial fibrillation

2018 ◽  
pp. 71-76 ◽  
Author(s):  
S. V. Grigoryan ◽  
L. G. Azarapetyan ◽  
K. G. Adamyan
Keyword(s):  
Atrial Fibrillation ◽  
Growth Factor ◽  
Structural Changes ◽  
Transforming Growth Factor ◽  
Matrix Metalloproteases ◽  
Diagnostic Methods ◽  
Atrial Fibrosis ◽  
Non Invasive ◽  
Level Measurement

Atrial fibrillation is the most prevalent arrhythmia, and tends to progress. Any structural changes in the heart may lead to its progressive remodelling with increased deposition of connective tissue and fibrosis. Predominance of collagen types I and III synthesis over its degradation leads to accumulation of fibers and to fibrosis. Increase of atrial fibrosis is usually found on autopsy and biopsy. There is relation revealed, of atrial fibrosis grade and postsurgery atrial fibrillation. The mechanisms participating in the structural remodelling and progression of atrial fibrosis are not studied well enough, but there is known role of renin-angiotensinaldosterone system, transforming growth factor, inflammation and matrix metalloproteases. As an alternative, one should consider non-invasive diagnostic methods: magnetic resonance imaging of the heart and biomarkers level measurement. Hyperactivation of the renin-angiotensin-aldosterone system facilitates structural remodelling of the heart and progression of atrial fibrosis. Hyperexpression of the transforming growth factor leads to selective atrial fibrosis, heterogeneity of excitation conduction and fibrillation onset. Matrix metalloproteases are the marker of extracellular degradation. Study of fibrosis biomarkers makes it to increase significantly the efficacy of atrial fibrillation course prediction.

Role of molecular signaling pathways in the pathogenesis of adenomyosis

2021 ◽  
Vol 70 (3) ◽  
pp. 121-134
Author(s):  
Maria A. Shalina ◽  
Maria I. Yarmolinskaya ◽  
Elena A. Netreba ◽  
Alexandra K. Beganova
Keyword(s):  
Drug Therapy ◽  
Growth Factor ◽  
Signaling Pathways ◽  
Transforming Growth Factor ◽  
Reproductive Function ◽  
Current Data ◽  
Diagnostic Methods ◽  
Molecular Signaling ◽  
Non Invasive

The prevalence of genital endometriosis and adenomyosis, in particular, is tending to increase. The lack of a complete understanding of the pathogenetic mechanisms and multifactorial causes of adenomyosis, the low effectiveness of existing drug therapy, and the importance of preserving reproductive function make it necessary to further study the pathogenesis of the disease, search for new non-invasive highly informative diagnostic methods and develop a new strategy for pathogenically based drug therapy. The review presents current data on the role of signaling pathways in the pathogenesis of the development of adenomyosis based on domestic and foreign literature sources retrieved from the electronic databases PubMed, CyberLeninka, and Google Scholar in the period from 1999 to 2020. Considerable emphasis is placed on the discussion of the research results in recent years. Based on the analysis, the role of transforming growth factor (TGF), vascular endothelial growth factor (VEGF), dual-specificity protein phosphatase (PTEN), Notch receptors, and eukaryotic translation initiation factors (eIFs) in the signaling of adenomyosis is presented. Further advanced study of signaling pathways in the pathogenesis of adenomyosis will allow developing highly specific and highly sensitive markers for non-invasive diagnostics, as well as new directions for drug treatment of the disease.

Abstract 251: Development of a Transgenic Goat Model with Cardiac-Specific Overexpression of Transforming Growth Factor-β1 to Study the Relationship Between Atrial Fibrosis and Atrial Fibrillation

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Irina A Polejaeva ◽  
Justin Hall ◽  
Qinggang Meng ◽  
Xinchang Zhou ◽  
Benjamin R Sessions ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Large Animal ◽  
Atrial Pacing ◽  
Atrial Fibrosis ◽  
Transgenic Goat ◽  
Large Animal Models ◽  
Fetal Fibroblasts ◽  
Tgf Β1

Studies on patients, large animal models and transgenic mouse models have shown a strong association of atrial fibrosis with atrial fibrillation (AF). However, it is unclear whether there is a causal relationship between atrial fibrosis and AF or whether these events appear as a result of independent pathological changes in the heart. We are testing the hypothesis that goats that overexpress TGF-β1 (transforming growth factor beta1) specifically in cardiac myocytes will develop atrial fibrosis that in turn will lead to AF. Many aspects of AF-related remodeling have been studied comprehensively in goat models. However, these AF models are typically mechanically induced (eg, the rapid atrial pacing model). This unique transgenic goat model has the potential to offer insights into the role of fibrosis in AF initiation and progression without the confounding effects of mechanical AF induction. Somatic cell nuclear transfer (SCNT or cloning) was used to produce TGF-β1 transgenic pregnancies. First, pcDNA3.1DV5-MHC-TGF-β1cys33ser vector was constructed by subcloning the MHC-TGF-β1 fragment from the plasmid pUC-BM20-MHC-TGF-β1 into the pcDNA3.1D V5 vector. The NeonTM transfection system was used to electroporate primary goat fetal fibroblasts. After two weeks of G418 selection, the resulting G418 resistant colonies were screened by PCR to confirm transgene integration into goat genomic DNA. PCR positive cells were used for SCNT. Cloned embryos (n=264) were cultured for 12-60 h in vitro and then transferred into synchronized recipient females (n=15). Confirmation of pregnancy was done by ultrasonography on day 30 post-transfer. At the time of this abstract submission, 40% (6/15) of recipients were confirmed to be pregnant as determined by the presence of a heartbeat. The range for the stage of gestation is between day-60 and day-120. The first delivery date is April 28, 2012. Several reports documented no pregnancy losses after 30 days of gestation in goats. Therefore, we expect that most if not all of these pregnancies will result in delivery of live offspring. To our knowledge, this will be the first transgenic goat model generated for cardiovascular research.

scholarly journals MG53/CAV1 regulates transforming growth factor-β1 signaling-induced atrial fibrosis in atrial fibrillation

Cell Cycle ◽  
2020 ◽  
Vol 19 (20) ◽  
pp. 2734-2744
Author(s):  
Meixia Zhang ◽  
Hechuan Wang ◽  
Xiaowen Wang ◽  
Mengjun Bie ◽  
Kai Lu ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Atrial Fibrosis

LOXL2 Inhibitor Attenuates Angiotensin II-Induced Atrial Fibrosis and Vulnerability to Atrial Fibrillation through Inhibition of Transforming Growth Factor Beta-1 Smad2/3 Pathway

2021 ◽  
pp. 1-11
Author(s):  
Yingbiao Wu ◽  
Jin Can ◽  
Shuwen Hao ◽  
Xun Qiang ◽  
Zhongping Ning
Keyword(s):  
Atrial Fibrillation ◽  
Angiotensin Ii ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Specific Inhibitor ◽  
Matrix Remodeling ◽  
Ang Ii ◽  
Atrial Fibrosis ◽  
Growth Factor Beta

<b><i>Objectives:</i></b> Angiotensin II (Ang II)-induced atrial fibrosis plays a vital role in the development of atrial fibrillation (AF). Lysyl oxidase-like 2 (LOXL2) plays an essential role in matrix remodeling and fibrogenesis, indicating it may involve fibrosis-associated diseases. This study aims to elucidate the role of LOXL2 in AF, and its specific inhibitor can suppress Ang II-induced inflammatory atrial fibrosis and attenuate the enhanced vulnerability to AF. <b><i>Methods:</i></b> Male mice C57BL/6 were subcutaneously infused with either saline or Ang II (2 mg/kg/day) for 4 weeks. DMSO or LOXL2 inhibitor LOXL2-IN-1 hydrochloride (LOXL2-IN-1) at a dose of 100 μg/kg/day were intraperitoneally injected once daily for 4 weeks. Morphological, histological, and biochemical analyses were performed. AF was induced by transesophageal burst pacing in vivo. <b><i>Results:</i></b> Expression of LOXL2 was increased in serum of AF patients and Ang II-treated mice. LOXL2-IN-1 significantly attenuated Ang II-induced AF vulnerability, cardiac hypertrophy, atrial inflammation, and fibrosis. LOXL2-IN-1 suppressed Ang II-induced expression of transforming growth factor beta-1 (TGF-β1) and collagen I and phosphorylation of Smad2/3 in atrial tissue. <b><i>Conclusions:</i></b> LOXL2 is a target of AF, and its inhibitor prevents atrial fibrosis and attenuated enhanced vulnerability to AF potentially through the TGF-β/Smad pathway.

The Role of Platelet-Derived Growth Factor-B/Platelet-Derived Growth Factor Receptor-β Signaling in Chronic Atrial Fibrillation

Cardiology ◽  
2016 ◽  
Vol 133 (4) ◽  
pp. 242-256 ◽  
Author(s):  
Zhiyuan Jiang ◽  
Guoqiang Zhong ◽  
Lina Wen ◽  
Yujie Hong ◽  
Shu Fang ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Growth Factor ◽  
Growth Factor Receptor ◽  
Chronic Atrial Fibrillation ◽  
Platelet Derived Growth Factor ◽  
Right Atrial ◽  
Type I ◽  
Atrial Fibrosis ◽  
Factor B

Objective: To explore the role of platelet-derived growth factor-B (PDGF-B)/platelet-derived growth factor receptor-β (PDGFR-β) signaling in chronic atrial fibrillation (AF). Methods: Thirty-nine AF patients and 33 patients with sinus rhythm (SR) were enrolled. Twenty canines were randomized into 5 groups: control, sham and AF lasting 1, 2 or 4 weeks. The AF canine models were made by rapid atrial pacing. Rat atrial fibroblasts were treated with PDGF-BB or PDGF-BB + PDGFR inhibitor AG1295, respectively. Gene expression in the right atrial appendage of patients, the left atrium of canines and rat atrial fibroblasts was measured by quantitative real-time PCR and Western blot, respectively. The degree of atrial fibrosis was evaluated by Masson trichrome staining. Results: The degree of atrial fibrosis and the expression of PDGF-B, PDGFR-β and collagen type I (COL1) in AF patients significantly increased compared to patients with SR. The degree of atrial fibrosis and the expression of PDGF-B and COL1 in canines increased progressively with the increased duration of AF. The expression of PDGFR-β increased progressively 2 weeks after AF. PDGF-BB promoted the proliferation and COL1 secretion of rat atrial fibroblasts. AG1295 attenuated these effects. Conclusions: Our study suggests that PDGF-B/PDGFR-β signaling, which promotes the proliferation and COL1 secretion of atrial fibroblasts, is an important contributor to atrial fibrosis in AF and may represent a novel target for the intervention of AF.

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