Differences in atrial fibrillation-associated proteins between the left and right atrial appendages from patients with rheumatic mitral valve disease: A comparative proteomic analysis

Liu, Hai; Chen, Guangxian; Zheng, Hongsheng; Han, Qin; Liang, Mengya; Feng, Kangni; Wu, Zhongkai

doi:10.3892/mmr.2016.5776

“…Table- 7 ), only LA (Supp. Table- 8 ), and RA + LA to evaluate how AFib develops in the molecular stage [ 19 ]. In our study, molecular aspects of transcriptomics give a foresight about the influences of persistent AFib on human atrial tissues.…”

Section: Resultsmentioning

confidence: 99%

Molecular Signatures of Human Chronic Atrial Fibrillation in Primary Mitral Regurgitation

Deniz

¹

,

Durdu

²

,

Doğan

³

et al. 2021

Cardiovascular Therapeutics

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Objectives. Transcriptomics of atrial fibrillation (AFib) in the setting of chronic primary mitral regurgitation (MR) remains to be characterized. We aimed to compare the gene expression profiles of patients with degenerative MR in AFib and sinus rhythm (SR) for a clearer picture of AFib pathophysiology. Methods. After transcriptomic analysis and bioinformatics ( n = 59 ), differentially expressed genes were defined using 1.5-fold change as the threshold. Additionally, independent datasets from GEO were included as meta-analyses. Results. QRT-PCR analysis confirmed that AFib persistence was associated with increased expression molecular changes underlying a transition to heart failure (NPPB, P = 0.002 ; ANGPTL2, P = 0.002 ; IGFBP2, P = 0.010 ), structural remodeling including changes in the extracellular matrix and cellular stress response (COLQ, P = 0.003 ; COMP, P = 0.028 ; DHRS9, P = 0.038 ; CHGB, P = 0.038 ), and cellular stress response (DNAJA4, P = 0.038 ). Furthermore, AFib persistence was associated with decreased expression of the targets of structural remodeling (BMP7, P = 0.021 ) and electrical remodeling (CACNB2, P = 0.035 ; MCOLN3, P = 0.035 ) in both left and right atrial samples. The transmission electron microscopic analysis confirmed ultrastructural atrial remodeling and autophagy in human AFib atrial samples. Conclusions. Atrial cardiomyocyte remodeling in persistent AFib is closely linked to alterations in gene expression profiles compared to SR in patients with primary MR. Study findings may lead to novel therapeutic targets. This trial is registered with ClinicalTrials.gov identifier: NCT00970034.

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“…This compartment specific phenomenon is not surprising given that differential expression of proteins has been reported in normal fetal heart [ 29 ]. In fact, it has been shown that the mRNA expression of BNP is increased in the atrium, but not ventricle, of streptozotocin-induced diabetic pigs [ 30 ]. Thus, it is not surprising that alterations in proteins can differ between chambers in various disease states, not just DCM.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, it is not surprising that alterations in proteins can differ between chambers in various disease states, not just DCM. For example, this phenomenon has been observed with atrial fibrillation [ 30 ], during experimental heart failure [ 31 , 32 ], and in children with congenital heart disease [ 33 ]. Alternatively, this compartment differential suggests that CCDC47 protein is upregulated in the atrium earlier, perhaps more rapidly, than in the ventricle.…”

Section: Discussionmentioning

confidence: 99%

Dysregulation of the calcium handling protein, CCDC47, is associated with diabetic cardiomyopathy

Thapa¹,

Wu²,

Sarma³

et al. 2018

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BackgroundDiabetes mellitus is associated with an increased risk in diabetic cardiomyopathy (DCM) that is distinctly not attributed to co-morbidities with other vasculature diseases. To date, while dysregulation of calcium handling is a key hallmark in cardiomyopathy, studies have been inconsistent in the types of alterations involved. In this study human cardiomyocytes were exposed to an environmental nutritional perturbation of high glucose, fatty acids, and l-carnitine to model DCM and iTRAQ-coupled LC–MS/MS proteomic analysis was used to capture proteins affected by the perturbation. The proteins captured were then compared to proteins currently annotated in the cardiovascular disease (CVD) gene ontology (GO) database to identify proteins not previously described as being related to CVD. Subsequently, GO analysis for calcium regulating proteins and endoplasmic/sarcoplasmic reticulum (ER/SR) associated proteins was carried out.ResultsHere, we identified CCDC47 (calumin) as a unique calcium regulating protein altered in our in vitro nutritional perturbation model. The cellular and functional role of CCDC47 was then assessed in rat cardiomyocytes. In rat H9C2 myocytes, overexpression of CCDC47 resulted in increase in ionomycin-induced calcium release and reuptake. Of interest, in a diet-induced obese (DIO) rat model of DCM, CCDC47 mRNA expression was increased in the atrium and ventricle of the heart, but CCDC47 protein expression was significantly increased only in the atrium of DIO rats compared to lean control rats. Notably, no changes in ANP, BNP, or β-MHC were observed between DIO rats and lean control rats.ConclusionsTogether, our in vitro and in vivo studies demonstrate that CCDC47 is a unique calcium regulating protein that is associated with early onset hypertrophic cardiomyopathy.Electronic supplementary materialThe online version of this article (10.1186/s13578-018-0244-0) contains supplementary material, which is available to authorized users.

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“…Despite efforts to discover plasma biomarkers in MVD (5) and to identify the role of ion channels (6), the molecular mechanism of AF in MVD remains unclear. Recently, proteomics studies were performed to explore the mechanisms of AF (6)(7)(8)(9)(10). These studies identified the differential proteins (DPs) in the right and left atrial appendage of rheumatic MVD patients (6,7,9), or pathways including ketone body (8) or glutathione (10) metabolism and the peroxisome proliferator-activated receptor (PPAR) pathway (9,10), which are related to postoperative AF (8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

Biomarkers and key pathways in atrial fibrillation associated with mitral valve disease identified by multi-omics study

Li¹,

Chen²,

Hou³

et al. 2021

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Background: Mitral valve disease (MVD)-associated atrial fibrillation (AF) is one of the most common arrhythmias with an increased risk of thromboembolic events. This study aimed to identify the molecular mechanisms and possible biomarkers for chronic AF in MVD by using multi-omics methods.Methods: This prospective study enrolled patients with MVD (n=100) undergoing mitral valve replacement surgery. The patients were allocated into chronic AF and sinus rhythm (SR) groups. Plasma samples were collected preoperatively. Proteomics was performed with isobaric tags for relative and absolute quantitation (iTRAQ) to identify differential proteins (DPs) between the two groups. The selected DPs were then validated in a new cohort of patients by enzyme-linked immunosorbent assay (ELISA). A gas chromatography-mass spectrometer was used in the metabolomics study to identify differential metabolites (DMs). Bioinformatics analyses were performed to analyze the results.Results: Among the 447 plasma proteins and 322 metabolites detected, 57 proteins and 55 metabolites, including apolipoprotein A-I (ApoA-I), apolipoprotein A-II (ApoA-II), LIM domain only protein 7 (LMO7), and vitronectin (VN) were differentially expressed between AF and SR patients. Bioinformatics analyses identified enriched pathways related to AF, including peroxisome proliferator-activated receptor alpha (PPARα), the renin angiotensin aldosterone system (RAAS), galactose, biosynthesis of unsaturated fatty acids, and linoleic acid metabolism.Conclusions: Using integrated multi-omics technologies in MVD-associated AF patients, the present study, for the first time, revealed important signaling pathways, such as PPARα, as well as possible roles of other signaling pathways, including the RAAS and galactose metabolism to understand the molecular mechanism of MVD-associated AF. It also identified a large number of DPs and DMs. Some identified proteins and metabolites, such as ApoA-I, ApoA-II, LMO7, and VN, may be further developed as biomarkers for MVD-associated AF.

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Differences in atrial fibrillation-associated proteins between the left and right atrial appendages from patients with rheumatic mitral valve disease: A comparative proteomic analysis

Cited by 5 publications

References 36 publications

Molecular Signatures of Human Chronic Atrial Fibrillation in Primary Mitral Regurgitation

Molecular Signatures of Human Chronic Atrial Fibrillation in Primary Mitral Regurgitation

Dysregulation of the calcium handling protein, CCDC47, is associated with diabetic cardiomyopathy

Biomarkers and key pathways in atrial fibrillation associated with mitral valve disease identified by multi-omics study

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