Dataset Information

β-thalassemia plasma EVs proteomics

ABSTRACT: Here, we performed plasma extracellular vesicles (EVs) proteomics on 20 β-thalassemia major (TM) patients, 20 intermedia (TI) patients, and 20 healthy controls to explore the subgroup characteristics and the potential biomarkers. The proteome of paired plasma was analyzed in parallel to compare the biomarker potential of both specimens. We first described the pathophysiological characteristics of different subtypes. More significant immunity abnormalities and lipid metabolism was separately observed in patients with TI and TM, which was consistent with the results of paired plasma proteomics. A diagnostic model consisting of six proteins with subtyping potential was proposed. Of note, superior performance of plasma EVs on patient subgroup differentiating was shown than plasma, demonstrating the potential of secreted EVs for diagnosis of β-thalassemia patients.

ORGANISM(S): Homo Sapiens

SUBMITTER: Fuquan Yang

PROVIDER: PXD034548 | iProX | Wed Jun 15 00:00:00 BST 2022

REPOSITORIES: iProX

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Publications

Differential proteomic patterns of plasma extracellular vesicles show potential to discriminate β-thalassemia subtypes.

Li Na N Wu Bowen B Wang Jifeng J Yan Yumeng Y An Peng P Li Yuezhen Y Liu Yuning Y Hou Yanfei Y Qing Xiaoqing X Niu Lili L Ding Xiang X Xie Zhensheng Z Zhang Mengmeng M Guo Xiaojing X Chen Xiulan X Cai Tanxi T Luo Jianming J Wang Fudi F Yang Fuquan F

iScience 20230125 2

The observed specificity of β-thalassemia-subtype phenotypes makes new diagnostic strategies that complement current screening methods necessary to determine each subtype and facilitate therapeutic regimens for different patients. Here, we performed quantitative proteomics of plasma-derived extracellular vesicles (EVs) of β-thalassemia major (TM) patients, β-thalassemia intermedia (TI) patients, and healthy controls to explore subgroup characteristics and potential biomarkers. Plasma quantitativ ...[more]

PMID: 36824279

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Project description:Background: Acute coronary syndromes (ACS) are associated with aberrant gene expression and epigenetic mechanisms. In particular, de novo DNA methylation is typically linked to gene silencing, but its role in heart disease remains not fully understood. Extracellular vesicles (EVs) are active components in cellular communication for their ability to carry a plethora of signalling biomolecules, thus representing a promising new diagnostic/therapeutic approach in cardiovascular diseases (CVDs). Indeed, there is the need of novel biomarkers for ACS prediction and timely detection. Purpose: We hypothesized that specific epigenetic signals can be carried by EVs. In this regard, we isolated and characterized circulating EVs from ACS patients and evaluated their potential role to influence DNA methylation in target cells. Methods: Circulating EVs were recovered, by ultracentrifugation, from plasma samples of 19 ACS patients and 50 healthy subjects (HS). Nanoparticle tracking analysis (NTA) and western blot (WB) were used to confirm the EVs integrity and purity. Peripheral blood mononuclear cells (PBMCs) of volunteer donors were treated with both ACS and HS derived EVs and genomic DNA was extracted to perform epigenome wide analysis through Reduced Representation Bisulfite Sequencing. ShinyGO, PANTHER, and STRING tools were interrogated to perform GO and PPI network analyses. Flow Cytometry, qRT-PCR, and WB analysis were also performed to evaluate and validate both intra-vesicular and intra-cellular signals. Results: Plasma ACS-derived EVs showed a significant up-regulation of DNA methyltransferases (DNMTs) gene expression levels as compared to HS (P<0.001). Specifically, de novo methylation transcripts, as DNMT3A and DNMT3B were significantly increased in plasma ACS-EVs. DNA methylation analysis of PBMCs from volunteer donors treated with HS- and ACS-derived EVs showed that RNF166 and CCND3 genes resulted the most hyper- and hypo-methylated, respectively, after by ACS-EV treatment. In addition, PPI network analysis specifically evidenced the subnetwork with SRC, as a hub gene, connecting it to NOTCH1, FOXO3, CDC42, IKBKG, RXRA, DGKG, known as important genes already involved in the onset of CVDs. Surprising, other novel genes, BAIAP2, SYP, CHL1, and SHB, which were hypomethylated, were found significantly overexpressed in PBMCs (P<0.005), underlying the fundamental modulating properties of EV cargo in atherosclerosis. Conclusions: These findings support the significant role of ACS plasma-derived EVs, inducing de novo DNA methylation signals, and modulating specific signaling pathways in target cells.

Dataset Information

β-thalassemia plasma EVs proteomics

Publications

Differential proteomic patterns of plasma extracellular vesicles show potential to discriminate β-thalassemia subtypes.

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