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Compartmentalisation proteomics revealed endolysosomal protein network changes in goat model of atrial fibrillation

ABSTRACT: To identify the role of the endolysosomal (EL) protein network in atrial fibrillation (AF), we applied a newly developed organelle isolation method to the AF goat model. To accomplish the goal, we used proteomics, transcriptomics, integrated analysis, enzyme assays, electron tomography, and western blotting and identified several regulating EL proteins, related protein networks and pathways.

ORGANISM(S): Capra hircus

PROVIDER: GSE228289 | GEO | 2024/06/12

REPOSITORIES: GEO

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Compartmentalisation proteomics revealed endolysosomal protein network changes in a goat model of atrial fibrillation

Project description:The emerging roles of endolysosomes (EL) in AF have yet to be discovered, especially how the EL contribute to the development of AF within a slow time frame. To identify the EL role in AF, we applied proteomics, transcriptomics, integrated analysis, electron tomography, western blotting and enzyme assays. To understand the cellular and EL driven dominant pathways, in AF, we applied an organelle protein isolation method, that was previously developed by us (Ayagama et al,.2021) on to an AF goat model. Our findings include upregulation of AMPK pathway, EL-specific proteins that were not identified in the TL, such as GAA, DYNLRB1, CLTB, SIRT3, CCT2, and muscle specific HSPB2. The structural anomalies such as autophago-vacuole formation, irregularly stacked mitochondria, and glycogen deposition provide an insight into of the contribution of EL contribution and the related pathways and molecular mechanisms.

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Compartmentalisation proteomics revealed endolysosomal protein network changes in goat model of atrial fibrillation

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Atrial fibrillation is associated with altered left-to-right atria gene expression ratio: implications for arrhythmogenesis and thrombogenesis

Project description:Background: Atrial fibrillation (AF) causes atrial remodeling, and the left atrium (LA) is the favored substrate for maintaining AF. However, it remains unclear if AF remodels both atria differently and contributes to LA arrhythmogenesis and thrombogenesis. Results: AF was associated with differential LA-to-RA gene expression related to specific ion channels and pathways as well as upregulation of thrombogenesis-related genes in the LA appendage. Targeting the molecular mechanisms underlying the LA-to-RA difference and AF-related remodeling in the LA appendage may help provide new therapeutic options in treating AF and preventing thromboembolism in AF. Paired left atrial and right atrial specimens were obtained from 13 patients with persistent AF receiving valvular surgery. The Paired specimens were sent for microarray comparison. Selected results were validated by quantitative real time-PCR (q-PCR) and Western blotting. Ultrastructural changes in the atria were evaluated by immunohistochemistry.

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