Dataset Information

Changes in the proteome of platelets from patients with critical progression of COVID-19

ABSTRACT: Platelets, the smallest cells in human blood known for their role in primary haemostasis, are also able to interact with pathogens and play a crucial role in the immune response. In severe coronavirus disease 2019 (COVID-19) cases, platelets become over-activated, resulting in the release of granules, exacerbating inflammation and contributing to the cytokine storm. Here we utilize label-free shotgun proteomics approach to further elucidate the role of platelets in COVID-19 progression and to identify predictive biomarkers for disease outcome. Platelet proteome of the severely ill COVID-19 patients varied significantly from to healthy controls. Significant changes in the levels of proteins associated with protein folding were detected. In addition, a number of proteins with isomerase activity were found in the patient samples, which appear to exert an influence on platelet activity via non-genomic properties of glucocorticoid receptor (GR) and nuclear factor κ-light-chain-enhancer of activated B cells (NFkB). We also performed a comparison of proteins found exclusively in controls, survivors and non-survivors. CRP, CA-1, SAA2 and SEPPINA3 were found to be biomarker candidates in platelets, showing a significant increase in ICU patients.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Platelet, Platelet

DISEASE(S): Coronavirus Infectious Disease

SUBMITTER: Svitlana Rozanova

LAB HEAD: Prof. Katrin Marcus-Alic

PROVIDER: PXD041681 | Pride | 2023-10-24

REPOSITORIES: Pride

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Publications

Changes in the Proteome of Platelets from Patients with Critical Progression of COVID-19.

Wolny Monika M Rozanova Svitlana S Knabbe Cornelius C Pfeiffer Kathy K Barkovits Katalin K Marcus Katrin K Birschmann Ingvild I

Cells 20230901 17

Platelets, the smallest cells in human blood, known for their role in primary hemostasis, are also able to interact with pathogens and play a crucial role in the immune response. In severe coronavirus disease 2019 (COVID-19) cases, platelets become overactivated, resulting in the release of granules, exacerbating inflammation and contributing to the cytokine storm. This study aims to further elucidate the role of platelets in COVID-19 progression and to identify predictive biomarkers for disease ...[more]

PMID: 37681923

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Project description:In sickle cell disease, ischemia-reperfusion injury and intravascular hemolysis produce endothelial dysfunction and vasculopathy characterized by reduced nitric oxide (NO) and arginine bioavailability. Recent functional studies of platelets in patients with sickle cell disease reveal a basally activated state, suggesting that pathological platelet activation may contribute to sickle cell disease vasculopathy. Studies were therefore undertaken to examine transcriptional signaling pathways in platelets that may be dysregulated in sickle cell disease. We demonstrate and validate here the feasibility of comparative platelet transcriptome studies on clinical samples from single donors, by the application of RNA amplification followed by microarray-based analysis of 54,000 probe sets. Data mining an existing microarray database, we identified 220 highly abundant genes in platelets and a subset of 72 relatively platelet-specific genes, defined by more than 10-fold increased expression compared to the median of other cell types in the database with amplified transcripts. The highly abundant platelet transcripts found in the current study included 82% or 70% of platelet abundant genes identified in two previous gene expression studies on non-amplified mRNA from pooled or apheresis samples, respectively. On comparing the platelet gene expression profiles in 18 patients with sickle cell disease in steady state to 12 African American controls, at a 3-fold cut-off and 5% false discovery rate, we identified ~100 differentially expressed genes, including multiple genes involved in arginine metabolism and redox homeostasis. Further characterization of these pathways using real time PCR and biochemical assays revealed increased arginase II expression and activity and decreased platelet polyamine levels. These studies suggest a potential pathogenic role for platelet arginase and altered arginine and polyamine metabolism in sickle cell disease and provide a novel framework for the study of disease-specific platelet biology. Experiment Overall Design: There are 18 sickle cell samples and 12 control samples from healthy African American volunteers.

Dataset Information

Changes in the proteome of platelets from patients with critical progression of COVID-19

Publications

Changes in the Proteome of Platelets from Patients with Critical Progression of COVID-19.

Similar Datasets

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