Dataset Information

Discovery of potential biomarkers in plasma-derived extracellular vesicles of a heart-transplanted chronic Chagas disease patient

ABSTRACT: Chagas disease (CD) is emerging in nonendemic countries. Biomarkers for earlier therapeutic response assessment in chronic CD patients are much needed. Here, we describe the first proteomic profiling of plasma-derived extracellular vesicles from a heart-transplanted patient with chronic CD and show the potential of this approach for discovering such biomarkers.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human) Trypanosoma Cruzi

TISSUE(S): Blood Plasma

DISEASE(S): Chagas Disease

SUBMITTER: Maria Tays Mendes

LAB HEAD: Igor Almeida

PROVIDER: PXD014668 | Pride | 2021-09-08

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	EV_Ch_04-02_fraction_A_2D_QEPlus_Run1.raw	Raw
	EV_Ch_04-02_fraction_B_2D_QEPlus_Run1.raw	Raw
	EV_Ch_04-02_fraction_C_2D_QEPlus_Run1.raw	Raw
	EV_Ch_04_fraction_A_2D_QEPlus_Run1.raw	Raw
	EV_Ch_04_fraction_B_2D_QEPlus_Run1.raw	Raw

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Publications

Plasma-Derived Extracellular Vesicles as Potential Biomarkers in Heart Transplant Patient with Chronic Chagas Disease.

Cortes-Serra Nuria N Mendes Maria Tays MT Mazagatos Clara C Segui-Barber Joan J Ellis Cameron C CC Ballart Cristina C Garcia-Alvarez Ana A Gállego Montserrat M Gascon Joaquim J Almeida Igor C IC Pinazo María Jesús MJ Fernandez-Becerra Carmen C

Emerging infectious diseases 20200801 8

Chagas disease is emerging in countries to which it is not endemic. Biomarkers for earlier therapeutic response assessment in patients with chronic Chagas disease are needed. We profiled plasma-derived extracellular vesicles from a heart transplant patient with chronic Chagas disease and showed the potential of this approach for discovering such biomarkers. ...[more]

PMID: 32687028

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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.