scholarly journals Circulating proteomic patterns in AF related left atrial remodeling indicate involvement of coagulation and complement cascade

2018 ◽  
Author(s):  
Jelena Kornej ◽  
Petra Büttner ◽  
Elke Hammer ◽  
Beatrice Engelmann ◽  
Borislav Dinov ◽  
...  

AbstractBackgroundLeft atrial (LA) electro-anatomical remodeling and diameter increase in atrial fibrillation (AF) indicates disease progression and is associated with poor therapeutic success. Furthermore, AF leads to a hypercoagulable state, which in turn promotes the development of a substrate for AF and disease progression in the experimental setting. The aim of this study was to identify pathways associated with LA remodeling in AF patients using untargeted proteomics approach.MethodsPeripheral blood samples of 48 patients (62±10 years, 63% males, 59% persistent AF) undergoing AF catheter ablation were collected before ablation. 24 patients with left atrial low voltage areas (LVA), defined as <0.5 mV, and 24 patients without LVA were matched for age, gender and CHA2DS2-VASc score. Untargeted proteome analysis was performed using LC-ESI-Tandem mass spectrometry in a label free intensity based workflow. Significantly different abundant proteins were identified and used for pathway analysis and protein-protein interaction analysis.ResultsAnalysis covered 280 non-redundant circulating plasma proteins. The presence of LVA correlated with 30 differentially abundant proteins of coagulation and complement cascade (q<0.05).ConclusionsThis pilot proteomic study identified plasma protein candidates associated with electro-anatomical remodeling in AF and pointed towards an imbalance in coagulation and complement pathway, tissue remodeling and inflammation

PLoS ONE ◽  
2018 ◽  
Vol 13 (11) ◽  
pp. e0198461 ◽  
Author(s):  
Jelena Kornej ◽  
Petra Büttner ◽  
Elke Hammer ◽  
Beatrice Engelmann ◽  
Borislav Dinov ◽  
...  

2020 ◽  
Author(s):  
Bolin Wu ◽  
Haitao Shang ◽  
Xitian Liang ◽  
Huajing Yang Huajing Yang ◽  
Hui Jing ◽  
...  

Abstract Background: Hepatocellular carcinoma (HCC) poses a severe threat to human health. The NET-1 protein has been proved to be strongly associated with HCC proliferation and metastasis in our previous study. Methods: Here, we developed a label-free proteome mass spectrometry workflow to analyze formalin-fixed and paraffin-embedded HCC xenograft samples collected in our previous study. Results: The result showed that 78 proteins were differentially expressed after NET-1 protein inhibited. Among them, the expression of 61 proteins up-regulated and the expression of 17 proteins were significantly down-regulated. Of the differentially expressed proteins, the vast majority of Gene Ontology enrichment terms belong to the biological process. The KEGG pathway enrichment analysis showed that the 78 differentially expressed proteins significantly enriched in 45 pathways. We concluded that the function of the NET-1 gene is not only to regulate HCC but also to participate in a variety of biochemical metabolic pathways in the human body. Furthermore, the protein-protein interaction analysis indicated that the interactions of differentially expressed proteins are incredibly sophisticated. All the protein-protein interactions happened after the NET-1 gene has been silenced. Conclusions: Finally, our study also provides a useful proposal for targeted therapy based on tetraspanin proteins to treat HCC, and further mechanism investigations are needed to reveal a more detailed mechanism of action for NET-1 protein regulation of HCC.


Proteomes ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 26
Author(s):  
Juthamard Chantaraamporn ◽  
Voraratt Champattanachai ◽  
Amnart Khongmanee ◽  
Chris Verathamjamras ◽  
Naiyarat Prasongsook ◽  
...  

Colorectal cancer (CRC) is a major cause of cancer mortality. Currently used CRC biomarkers provide insufficient sensitivity and specificity; therefore, novel biomarkers are needed to improve the CRC detection. Label-free quantitative proteomics were used to identify and compare glycoproteins, enriched by wheat germ agglutinin, from plasma of CRC patients and age-matched healthy controls. Among 189 identified glycoproteins, the levels of 7 and 15 glycoproteins were significantly altered in the non-metastatic and metastatic CRC groups, respectively. Protein-protein interaction analysis revealed that they were predominantly involved in immune responses, complement pathways, wound healing and coagulation. Of these, the levels of complement C9 (C9) was increased and fibronectin (FN1) was decreased in both CRC states in comparison to those of the healthy controls. Moreover, their levels detected by immunoblotting were validated in another independent cohort and the results were consistent with in the study cohort. Combination of CEA, a commercial CRC biomarker, with C9 and FN1 showed better diagnostic performance. Interestingly, predominant glycoforms associated with acetylneuraminic acid were obviously detected in alpha-2 macroglobulin, haptoglobin, alpha-1-acid glycoprotein 1, and complement C4-A of CRC patient groups. This glycoproteomic approach provides invaluable information of plasma proteome profiles of CRC patients and identification of CRC biomarker candidates.


2016 ◽  
Vol 2016 ◽  
pp. 1-5
Author(s):  
Naoko Hijioka ◽  
Masashi Kamioka ◽  
Hitoshi Suzuki ◽  
Yasuchika Takeishi

Introduction. Little is known about the effects of volume change by hemodialysis (HD) and mechanical stress caused by an anatomical structure being in contact with the left atrium on the progression of atrial remodeling. We experienced a case of atrial tachycardia (AT) in a patient who had left atrial (LA) scarring at the LA roof and a low-voltage area with slow conduction around the LA scar as components of AT circuit. Here, we present the conceivable hypothesis of the LA scar and the low-voltage area formation. Our concept can be useful in developing a strategy for ablation in a patient with chronic renal failure (CRF) on HD.Case Report. A 65-year-old man with CRF on HD was referred for AT ablation. Three-dimensional electroanatomical mapping revealed that the AT conducted around an LA scar in a counterclockwise fashion. There was a slow conduction area at the superior side of the LA scar, where the AT was terminated during the ablation. Computed tomography indicated a close relationship between the LA and the anatomical structures (ascending aorta and pulmonary artery).Conclusion. Volume change by HD and close contact of anatomical structures to the LA can promote atrial remodeling, resulting in AT occurrence.


2020 ◽  
Author(s):  
Feiyu Wei ◽  
Li Lv ◽  
Xiaohui Kuang ◽  
Wenjun Ren ◽  
Jie Fan

Abstract Background: Progression of atrial fibrosis is vital for atrial remodeling in atrial fibrillation (AF). The main objective of this study was to explore the association between miR-144-3p and miR-425-5p, and atrial fibrosis as well as the resultant impact on atrial remodeling in AF.Methods and Results: Through miRNAs sequencing and qRT-PCR, we demonstrated that miR-144-3p and miR-425-5p were downregulated in plasma and atrial tissue among the patients who suffered from AF. We confirmed that the plasma’s miRNAs level was negatively correlated with left atrial fibrosis, which was evaluated with the left low voltage area using left atrial voltage matrix mapping. Catheter ablation restored decreased plasma miR-144-3p and miR-425-5p. Besides, ROC curve analysis revealed that the miRNAs not only differentiated AF from healthy control of AUC 0.928 and 0.921, respectively, but also discriminated persistent AF from paroxysmal AF of AUC 0.906 and 0.888, respectively. Furthermore, the downregulated miR-144-3p and miR-425-5p promoted atrial fibroblast proliferation by CCK-8. CREB1 was realized to be a common direct target for miR-144-3p and miR-425-5p by western blot and luciferase assay.Conclusions: Our findings suggested that miR-144-3p and miR-425-5p could serve as novel atrial fibrosis biomarkers and hence contribute to atrial remodeling in AF.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
Y Takahashi ◽  
T Kitai ◽  
T Watanabe ◽  
T Fujita

Abstract Background Low-voltage zone (LVZ) in the left atrium (LA) seems to represent fibrosis. LA longitudinal strain assessed by speckle tracking method is known to correlate with the extent of fibrosis in patients with mitral valve disease. Purpose We sought to identify the relationship between LA longitudinal strain and LA bipolar voltage in patients with atrial fibrillation (AF). We tested the hypothesis that LA strain can predict LA bipolar voltage. Methods A total of 96 consecutive patients undergoing initial AF ablation were analyzed. All patients underwent transthoracic echocardiography including 2D speckle tracking measurement on the day before ablation during sinus rhythm (SR group, N=54) or during AF (AF group, N=42). LA longitudinal strain was measured at basal, mid, and roof level of septal, lateral, anterior, and inferior wall in apical 4- and 2-chamber view. Global longitudinal strain (GLS) was defined as an average value of the 12 segments. LA voltage map was created using EnSite system, and global mean voltage was defined as a mean of bipolar voltage of the whole LA excluding pulmonary veins and left atrial appendage. LVZ was defined as less than 1.0 mV. Results There was a significantly positive correlation between GLS and global mean voltage (r=0.708, p&lt;0.001). Multivariate regression analysis showed that GLS and age were independent predictors of global mean voltage. There was a significant negative correlation between global mean voltage and LVZ areas. Conclusions There was a strong correlation between LA longitudinal strain and LA mean voltage. GLS can independently predict LA mean voltage, subsequently LVZ areas in patients with AF. Funding Acknowledgement Type of funding source: None


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