Proteomic sequencing of atrial fibrosis rat model caused by chronic intermittent hypoxia
Ontology highlight
ABSTRACT:
ORGANISM(S): Rattus Norvegicus
SUBMITTER: 
Xue Liang
PROVIDER: PXD042312 | iProX | Thu May 18 00:00:00 BST 2023
REPOSITORIES: iProX
Similar Datasets
Project description:Objectives: We studied the signal transduction of atrial structural remodelling that contributes to the pathogenesis of atrial fibrillation (AF). Backround: Fibrosis is a hallmark of arrhythmogenic structural remodelling but the underlying molecular mechanisms are incompletely understood. Methods: We performed transcriptional profiling of left atrial myocardium (LA) from patients with AF and sinus rhythm (SR) and applied cultured primary cardiac cells and transgenic mice with overexpression of constitutively active V12Rac1 (RacET) who develop AF at old age to characterize mediators of the signal transduction of atrial remodeling. Results: LA from patients with AF showed a marked upregulation of connective tissue growth factor (CTGF) expression compared SR patients. This was associated with increased fibrosis, NADPH-oxidase-, Rac1- and RhoA activity, upregulation of N-cadherin and connexin 43 (Cx43) expression and increased angiotensin II tissue concentration. In neonatal rat cardiac myocytes and -fibroblasts, a specific small molecule inhibitor of Rac1 or simvastatin completely prevented the angiotensin II induced upregulation of CTGF, Cx43 and N-cadherin expression. Transfection with small-inhibiting CTGF RNA blocked Cx43 and N-cadherin expression. RacET mice showed upregulation of CTGF, Cx43 and N-cadherin protein expression. Inhibition of Rac1 by oral statin treatment prevented these effects, identifying Rac1 as a key regulator of CTGF in vivo. Conclusion: The data identify CTGF as an important mediator of atrial structural remodelling during AF. Angiotensin II activates CTGF via activation of Rac1 and NADPH oxidase, leading to upregulation of Cx43, N-cadherin and interstitial fibrosis and therefore contributing to the signal transduction of atrial structural remodelling. Array design study consists of 5 Atrial Fibrillation patients and matched 5 samples of patients in sinus rhythm (controls).
2010-02-21 | E-GEOD-14975 | biostudies-arrayexpress
Project description:Background Atrial fibrosis plays a critical role in the development of atrial fibrillation (AF). Exosome is a promising cell-free therapeutic approach for the treatment of AF. The purpose of this study was to explore the mechanisms underlying exosomes derived from atrial myocytes regulated atrial remodeling and ask whether their manipulation allows for therapeutic modulation of fibrosis potential abnormalities during AF. Methods We isolated exosomes from atrial myocytes and patients serum, microRNA (miRNA) sequencing analyzed the exosomal miRNAs in atrial myocytes-exosomes and patients serum-exosomes. mRNA sequencing and bioinformatics analysis corroborate the key gene as direct targets of miR-210-3p. Results The miRNAs sequencing analysis identified that miR-210-3p expression significantly increased in exosomes of tachypacing atrial myocytes and serum of AF patients. In vitro, the analysis showed that miR-210-3p inhibitor reversed tachypacing-induced proliferation and collagen synthesis in atrial fibroblasts. Accordingly, KO miR-210-3p could reduce the incidence of AF and ameliorate atrial fibrosis induced by Ang Ⅱ. The mRNA sequencing analysis and Dual-Luciferase reporter assay proved that glycerol-3-phosphate dehydrogenase 1-like (GPD1L) is the potential target gene of miR-210-3p. The functional analysis suggests that GPD1L regulated atrial fibrosis via PI3K/AKT signaling pathway. Besides, silencing GPD1L in atrial fibroblasts induced cells proliferation and these effects could be reversed by PI3K inhibitor (LY294002). Conclusion We demonstrate that atrial myocytes-derived exosomal miR-210-3p promoted the proliferation and collagen synthesis via inhibiting GPD1L in atrial fibroblasts. Preventing pathological crosstalk between atrial myocytes and fibroblasts may be as a novel target to improve atrial fibrosis in AF.
2022-08-17 | GSE210894 | GEO
Project description:Atrial fibrillation (AF) remains challenging to prevent and treat. It is associated with increased rates of heart failure, stroke and neurological decline. A key feature of AF is atrial enlargement. However, not all atrial enlargement progresses to pathology and AF.
In the current study, we characterized mouse atria from a 1) pathological model (cardiac-specific transgenic (Tg) that develops dilated cardiomyopathy [DCM] and AF due to reduced protective signalling [PI3K]; DCM-dnPI3K), and a 2) physiological model (cardiac-specific Tg with an enlarged heart due to increased insulin-like growth factor 1 receptor; IGF1R). Atrial enlargement in the DCM-dnPI3K Tg, but not IGF1R Tg, was associated with atrial dysfunction, fibrosis and a heart failure gene expression pattern. Proteomics analysis identified proteins and pathways that were differentially regulated in pathological and physiological atrial enlargement, and provides a resource to study potential drug targets for AF.
2023-12-07 | MSV000093605 | MassIVE
Project description:Myocardial interstitial fibrosis is a common thread in multiple cardiovascular diseases including heart failure, atrial fibrillation, conduction disease and sudden cardiac death. To investigate the biologic pathways that underlie interstitial fibrosis in the human heart, we developed a machine learning model to measure myocardial T1 time, a marker of myocardial interstitial fibrosis, in 41,505 UK Biobank participants. Greater T1 time was associated with diabetes mellitus, renal disease, aortic stenosis, cardiomyopathy, heart failure, atrial fibrillation, conduction disease and rheumatoid arthritis. Mendelian randomization analysis supported a potential causal role for diabetes mellitus type 1 in myocardial interstitial fibrosis. In genome-wide association analysis, we identified 11 independent loci associated with native myocardial T1 time. The identified loci implicated genes involved in glucose transport (SLC2A12), iron homeostasis (HFE, TMPRSS6), tissue repair (ADAMTSL1, VEGFC), oxidative stress (SOD2), cardiac hypertrophy (MYH7B) and calcium signaling (CAMK2D). Transcriptome-wide association studies highlighted the role of expression of ADAMTSL1 and SLC2A12 in human cardiac tissue in modulating myocardial interstitial fibrosis. Using a TGFβ1-mediated cardiac fibroblast activation assay, we found that 9 out of the 11 genome-wide significant loci comprised genes that exhibited temporal changes in expression and/or open chromatin conformation supporting the biological relevance of these loci to myocardial fibrosis and myofibroblast cell state acquisition. Harnessing machine learning to perform large-scale phenotyping of interstitial fibrosis in the human heart, our results yield novel insights into biologically relevant pathways to myocardial fibrosis and prioritize a number of pathways for further investigation.
2023-03-11 | GSE225336 | GEO
Project description:This study will report the incidence of atrial fibrillation after elective colorectal cancer resection in the over 65 age group. This will be used to validate a risk model for the development of post-operative atrial fibrillation.
Eligible patients will undergo electrocardiogram based screening for atrial fibrillation, as well as brain natriuretic peptide tests prior to surgery. They will undergo 24 hour holter monitor prior to surgery, and at 30 and 90 days following surgery.
The primary outcome will be occurrence of atrial fibrillation within 90 days of surgery. Secondary outcomes include quality of life change, use of hospital services for atrial fibrillation, and complications of atrial fibrillation. This will be used to validate the pre-existing model for prediction of atrial fibrillation.
| 2312263 | ecrin-mdr-crc
Project description:Objectives: We studied the signal transduction of atrial structural remodelling that contributes to the pathogenesis of atrial fibrillation (AF). Backround: Fibrosis is a hallmark of arrhythmogenic structural remodelling but the underlying molecular mechanisms are incompletely understood. Methods: We performed transcriptional profiling of left atrial myocardium (LA) from patients with AF and sinus rhythm (SR) and applied cultured primary cardiac cells and transgenic mice with overexpression of constitutively active V12Rac1 (RacET) who develop AF at old age to characterize mediators of the signal transduction of atrial remodeling. Results: LA from patients with AF showed a marked upregulation of connective tissue growth factor (CTGF) expression compared SR patients. This was associated with increased fibrosis, NADPH-oxidase-, Rac1- and RhoA activity, upregulation of N-cadherin and connexin 43 (Cx43) expression and increased angiotensin II tissue concentration. In neonatal rat cardiac myocytes and -fibroblasts, a specific small molecule inhibitor of Rac1 or simvastatin completely prevented the angiotensin II induced upregulation of CTGF, Cx43 and N-cadherin expression. Transfection with small-inhibiting CTGF RNA blocked Cx43 and N-cadherin expression. RacET mice showed upregulation of CTGF, Cx43 and N-cadherin protein expression. Inhibition of Rac1 by oral statin treatment prevented these effects, identifying Rac1 as a key regulator of CTGF in vivo. Conclusion: The data identify CTGF as an important mediator of atrial structural remodelling during AF. Angiotensin II activates CTGF via activation of Rac1 and NADPH oxidase, leading to upregulation of Cx43, N-cadherin and interstitial fibrosis and therefore contributing to the signal transduction of atrial structural remodelling.
2010-02-11 | GSE14975 | GEO
Project description:Ischemic heart disease remains the leading cause of mortality and morbidity worldwide despite improved possibilities in medical care. Alongside interventional therapies, such as coronary artery bypass grafting (CABG), adjuvant tissue-engineered and cell-based treatments can provide regenerative improvement. Unfortunately, most of these advanced approaches require multiple lengthy and costly preparation stages without in turn delivering significant clinical benefit.
Here, we investigated the effect of epicardial matrix patch-encased atrial appendage micrografts (AAMs) in a mouse model of myocardial infarction. The matrix-covered AAM patches salvaged the myocardium from infarction-induced functional tissue loss. Fibrosis was attenuated, and site-targeted proteomics revealed AAM patch-activated pathways for angiogenesis and cardiogenesis. The matrix component of the graft further supports functional myocardial recovery by ventricular unloading.
The composite epicardial matrix graft encasing AAM micrografts delivers effects desirable for adjuvant cardiac therapy preserving functional cardiac tissue and restricting fibrosis after myocardial infarction.
2019-07-23 | MSV000084120 | MassIVE
Project description:Atrial fibrillation (AF) is the most common form of arrhythmia observed in clinical cardiac diseases. Angiotensin II (Ang II) and elevation of blood pressure have been considered to be the main risk regulators of AF. However, the time series proteome profiling and the key signaling pathways involved in the development of Ang II-induced AF remain unclear. Wild-type C57BL/6 male mice (10 weeks old) were infused with Ang II (2000 ng/kg/min) for 1, 2 and 3 weeks, respectively. AF inducibility, left atrial volume and fibrosis were examined by echocardiography and histological staining. The time series proteome in atria tissues was evaluated with Isobaric tags for relative and absolute quantitation (iTRAQ) and liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) technologies. This study defined the dynamic changes of the differentially expressed proteins (DEPs) involved in Ang II-induced AF, and identified that mitochondrial oxidative phosphorylation may play a key role in this disease. These findings provide a resource for understanding the molecular mechanism research of AF.
2022-04-04 | PXD022238 | Pride
Project description:To investigate how chromatin is shaped during inflammation geared towards the development of fibrosis in peritoneal tissue, we performed ATAC-seq in peritoneal membranes from wt and Il-6 knockout mice challenged with SES (a lyophilized cell-free supernatant prepared from Staphylococcus epidermidis ) together with Th1 polarised CD4+ T-cells administered via the intraperitoneal route. Peritoneal membrane was harvested 3 hours after injection, immediately snap-frozen in liquid nitrogen, and stored at -80C until processed. Tissues were diced and ground to a fine powder with intermittent addition of liquid nitrogen and Omni-ATAC-seq was performed.
2022-04-04 | E-MTAB-10739 | biostudies-arrayexpress