Dataset Information

Differential proteomic analysis of cardiac tissue in atrial fibrillation

ABSTRACT: Atrial fibrillation (AF) is the most common sustained arrhythmia characterized by rapid and multiple irregular excitations within the atria. AF is associated with serious morbidity and increased mortality, and its prevalence is prospected to increase as society ages. The limited therapeutic efficacy of AF treatment as well as its high socioeconomic burden makes AF a major clinical challenge. Despite our expanding knowledge of individual proteins and pathways involved in the complex pathophysiology of atrial fibrillation (AF), an unbiased overview of proteins and functionally enriched biological processes as well as their crosstalk is lacking. Here, we performed an explorative proteomics analysis to reveal the global abundance of proteins in cardiac tissue of patients, and deciphered functionally grouped gene ontologies (GO) to uncover a perspective of the disease biology driving or driven by AF. A total of 2703 proteins were identified by liquid chromatography coupled to tandem mass spectrometry. Among them, 150 proteins (accounting for 5.6% of 2703) had a significantly altered abundance (100 proteins increased and 50 decreased) in AF. A significant biological connection was found between those (protein-protein interaction enrichment p-value=1.0e-16). GO enrichment analysis showed that these 150 proteins were mainly located in extracellular/cytoplasmic vesicles, mitochondrion, and cytoskeletal compartments. Correspondingly, the 100 proteins increased in AF were significantly enriched in the GO terms related to immune system, metabolic process, iron process, ECM disassembly, mitochondrial translation and apoptotic signaling. Partially clustered proteins with dense functional link were found in immune system and metabolic process, and were respectively annotated in neutrophil degranulation, and oxoacid metabolic process coupled to the subunits of mitochondrial dehydrogenase NADH. Those processes enriched in AF had crosstalk via the proteins involved in neutrophil degranulation. Selected proteins such as LCN2 (neutrophil degranulation), CA3 (immune system), NDUFS2 (complex I) and MYH10 (actin motor protein) were validated by western blot or qPCR in an independent cohort. The 50 proteins decreased in AF were collectively enriched in vesicle-mediated transport and actin filament-based movement. We demonstrate that important biological processes underlying persistent AF as well as their crosstalk via the components of neutrophil degranulation. Our study provides a novel insight for a more efficient targeting strategy for AF treatment.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cardiac Muscle Tissue Of Atrium, Left Atrium

DISEASE(S): Atrial Fibrillation

SUBMITTER: Sander Piersma

LAB HEAD: Connie Ramona Jimenez

PROVIDER: PXD013230 | Pride | 2021-09-08

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	MaxQuantsearch.zip	Other
	QE1_170712_OPL5014_MK_EM_AFpilot_A1.raw	Raw
	QE1_170712_OPL5014_MK_EM_AFpilot_A2.raw	Raw
	QE1_170712_OPL5014_MK_EM_AFpilot_A3.raw	Raw
	QE1_170712_OPL5014_MK_EM_AFpilot_A5.raw	Raw

Items per page:

1 - 5 of 94

Publications

Neutrophil degranulation interconnects over-represented biological processes in atrial fibrillation.

Kawasaki Makiri M Meulendijks Eva R ER van den Berg Nicoline W E NWE Nariswari Fransisca A FA Neefs Jolien J Wesselink Robin R Baalman Sarah W E SWE Jongejan Aldo A Schelfhorst Tim T Piersma Sander R SR Pham Thang V TV van Boven Wim J P WJP Driessen Antoine H G AHG Jimenez Connie R CR de Groot Joris R JR

Scientific reports 20210203 1

Despite our expanding knowledge about the mechanism underlying atrial fibrillation (AF), the interplay between the biological events underlying AF remains incompletely understood. This study aimed to identify the functionally enriched gene-sets in AF and capture their interconnection via pivotal factors, that may drive or be driven by AF. Global abundance of the proteins in the left atrium of AF patients compared to control patients (n = 3/group), and the functionally enriched biological process ...[more]

PMID: 33536523

Similar Datasets

Project description:Single-walled carbon nanotubes (SWCNTs) are being explored and used for a wide range of applications in industrial and medical sectors, and the increasing exposure of SWCNTs necessitate the studies of their potential environmental and health effects. Considerable efforts have been made to improve the dispersion of SWCNTs by chemical modifications. The present study was designed to determine if the acid functionalization of SWCNTs enhanced the toxicity and more efforts were made to understand the molecular mechanisms. RAW264.7 cells were exposed to 0-100μg/mL of SWCNTs and AF-SWCNTs for 24 hours and cell proliferation, viability, and gene expression profiles were assessed and compared. Results showed that the magnitude of AF-SWCNT-induced cell proliferation inhibition was higher than that of SWCNTs. 10μg/mL of AF-SWCNTs was determined as non-toxic to cells by viability analysis. AF-SWCNTs could enter and aggregate in cell cytoplasm and nuclear areas. Microarray, real-time reverse-transcriptase polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assays (ELISA) demonstrated that AF-SWCNTs (1, 10, and 50μg/mL) altered gene and protein expression patterns. The most differentially expressed genes were related to pro-inflammatory cytokines and chemokines (such as CCL-3 and CCL-4), apoptosis (e.g., Caspase-1, -4, and Dffa), protective response (such as Hmox-1and GSTM3), and cell surface molecules such as ICAM-1, Itgb2, indicating a possible involvement of SWCNT in inflammation, anti-apoptotic and DNA fragmentation, carcinogenesis and biased T cell polarization. Furthermore, a substantial amount of down-regulated genes were found related to ribosomal assembly and mitochondrial respiration chain, implicating a possible mechanism of SWCNT-induced oxidative stress and gene expression inhibition. RAW264.7 gene expression after exposure to 1-50ug/ml AF-SWCNT-24 hours. 0ug/ml of AF-SWCNT was used as control sample. The data were obtained from three biological replicates.

Project description:Sjogren’s syndrome (SS) is characterized by dysfunctional mucous membranes and dysregulated moisture-secreting glands resulting in various symptoms, including dry mouth and dry eyes. Here, we wanted to profile and compare the tears and saliva proteomes of SS patients to healthy controls. Tear and saliva samples were collected and subjected to an isotopic dimethylation labeling shotgun proteomics workflow to identify alterations in protein levels. In tear samples, we identified 83 upregulated and 112 downregulated proteins. Altered pathways in SS patients’ tears included leukocyte transendothelial migration, neutrophil degranulation, and post-translation protein phosphorylation. In healthy controls’ tears, enriched proteins for glycolysis, amino acid metabolism and apoptotic signaling pathway were identified. In saliva, we identified 108 upregulated and 45 downregulated proteins. Altered pathways in SS patients’ saliva included cornification, sensory perception to taste and neutrophil degranulation. In healthy controls’ saliva, enriched proteins for JAK-STAT signaling after interleukin-12 stimulation, phagocytosis and glycolysis in senescence were identified. Dysregulated protease activity is implicated in the initiation of inflammation and immune cell recruitment in SS. We identified 20 proteases and protease inhibitors in tears and 18 in saliva which are differentially expressed between SS patients and healthy controls. Next, we quantified endogenous proteoglycan 4 (PRG4), a mucin-like glycoprotein previously shown to be present in tears and never studied in saliva, in tear wash and saliva samples via a bead-based immune assay. We identified decreased levels of PRG4 in SS patients’ tear wash compared to normal samples. Conversely, in saliva, we found elevated levels of PRG4 concentration and visualized PRG4 expression in human parotid gland via immunohistological staining. These findings improve our mechanistic understanding of the disease and changes in SS patients’ protein expression will help identify new potential drug targets. PRG4 is among the promising targets, which we identified here, in saliva, for the first time.