Proteomics

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Platelet-derived microparticles from obese individuals: characterization of number, size, proteomics and crosstalk with cancer and endothelial cells


ABSTRACT: Rationale. Obesity is a risk factor for atherothrombosis and various cancers. However, the mechanisms are not completely uncovered. Objectives. We aimed to verify whether the microparticles (MPs) released from thrombin-activated platelets differed in obese and nonobese women for number, size, and proteomics cargo and the capacity to modulate in vitro the expression of genes related to the epithelial to mesenchymal transition (EMT) and the endothelial to mesenchymal transition (EndMT), and COX-2, a pro-angiogenic pathway. Methods and Results. MPs were obtained from thrombin activated platelets of four obese women and their matched, lean controls . MPs were analyzed by cytofluorimeter and protein content by liquid chromatography-mass spectrometry. Obese MPs were not different in number but were characterized by increased heterogeneity in size. In obese individuals, MPs containing mitochondria (mitoMPs) expressed lower CD41 levels and increased phosphatidylserine associated with enhanced Factor V representing a signature of a prothrombotic state. Proteomics analysis identified 44 proteins downregulated and 3 upregulated in obese versus nonobese MPs . A reduction in the proteins involved in mitophagy and antioxidant defenses, and of the -granular membrane was detected in the MPs of obese individuals. MPs released from platelets of obese individuals were more prone to induce the expression of marker genes of EMT and EndMT when incubated with HT29 cells and human cardiac microvascular endothelial cells(HCMEC), respectively. A protein, highly enhanced in obese MPs, was the pro-platelet basic protein with pro-inflammatory and tumorigenic actions. MPs from obese, but not nonobese, women induced COX-2 in HCMEC. Conclusions. Platelet-derived MPs of obese women showed higher heterogeneity in size and contained different levels of proteins relevant to thrombosis and tumorigenesis. Obese MPs presented enhanced capacity to induce changes in the expression of EMT and EndMT markers and COX-2. These effects might contribute to the increased risk for the development of thrombosis and multiple malignancies in obesity.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Platelet, Blood Cell

DISEASE(S): Cardiovascular System Disease

SUBMITTER: Simone Marcone  

LAB HEAD: Professor Paola Patrignani

PROVIDER: PXD011563 | Pride | 2019-02-19

REPOSITORIES: Pride

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Publications

Platelet-Derived Microparticles From Obese Individuals: Characterization of Number, Size, Proteomics, and Crosstalk With Cancer and Endothelial Cells.

Grande Rosalia R   Dovizio Melania M   Marcone Simone S   Szklanna Paulina B PB   Bruno Annalisa A   Ebhardt H Alexander HA   Cassidy Hilary H   Ní Áinle Fionnuala F   Caprodossi Anna A   Lanuti Paola P   Marchisio Marco M   Mingrone Geltrude G   Maguire Patricia B PB   Patrignani Paola P  

Frontiers in pharmacology 20190122


<b>Rationale:</b> Obesity is a risk factor for atherothrombosis and various cancers. However, the mechanisms are not yet completely clarified. <b>Objectives:</b> We aimed to verify whether the microparticles (MPs) released from thrombin-activated platelets differed in obese and non-obese women for number, size, and proteomics cargo and the capacity to modulate <i>in vitro</i> the expression of (i) genes related to the epithelial to mesenchymal transition (EMT) and the endothelial to mesenchymal  ...[more]

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