Phosphoproteomic Fingerprint of Platelets in Obesity: Insights into Platelet Reactivity

M. Nuñez Barrachina¹, L. Hermida-Nogueira¹, L. A. Morán¹, V. Casas², S. M. Hicks³, A. M. Sueiro⁴, Y. Din⁵, R. K. Andrews³, E. E. Gardiner³, J. Abián², M. Carrascal², M. Pardo⁶, Á. García¹

¹University of Santiago de Compostela, Santiago de Compostela, Spain, ²IIBB-CSIC-IDIBAPS, CSIC/UAB Proteomic Laboratory, Barcelona, Spain, ³The Australian National University, 3ACRF Dept. Cancer Biology and Therapeutics. John Curtin School of Medical Research, Camberra, Australia, ⁴Servicio de Endocrinología, Xerencia de Xestión Integrada de Santiago (XXS), Santiago de Compostela, Spain, ⁵University of Birmingham, Institute of Cardiovascular Sciences, College of Medical and Dental Sciences,, Birmingham, United Kingdom, ⁶Instituto de Investigación Sanitaria de Santiago (IDIS), Grupo Obesidómica, Santiago de Compostela, Spain

Abstract Number: PB1718

Meeting: ISTH 2020 Congress

Theme: Platelets and Megakaryocytes » Platelet Proteomics and Genomics

Background: Obesity is associated with a pro-inflammatory and pro-thrombotic state that supports atherosclerosis progression.

Aims: The main goal of this study was to gain insights into the phosphorylation events related to platelet reactivity in obesity and identify platelet biomarkers and altered activation pathways in this clinical condition.

Methods: We recently performed a comparative phosphoproteomic analysis of resting platelets from obese patients and their age- and sex-matched lean controls. In the present study, we validate the phosphoproteomics data by targeted proteomics, mechanistic, functional and biochemical assays.

Results: Most of the altered phosphoproteins were involved in immunoreceptor tyrosine-based activation motif (ITAM)-based signalling pathways, cytoskeleton reorganization and vesicle transport. Interestingly, Src^Y419, VAMP8^S55, PKCθ^S695, LAT^S40/S43 were validated by targeted mass spectrometry in an additional cohort of patients showing increased levels of these phosphorylation sites in obesity. To confirm an alteration of ITAM-related signalling pathways, flow cytometry assays were performed in whole blood indicating higher surface levels of GPVI (p< 0.0001) and CLEC-2 (p< 0.05) in platelets from obese patients correlating positively with BMI. ROC curves analysis suggested a much higher sensitivity for GPVI (area=0.84) to discriminate between obese and lean individuals. Indeed, we also found that obese platelets displayed more adhesion to collagen-coated plates (p< 0.05). In line with the above data, sGPVI levels - indicative of higher GPVI signalling activation - were almost double in plasma from obese patients (p< 0.05).

Conclusions: In conclusion, our results provide novel information on platelet phosphorylation changes related to obesity, revealing the impact of this chronic pathology on platelet reactivity and pointing towards the main signalling pathways deregulated.

[Phosphoproteomic fingerprint of resting platelets in obesity: the main up-regulated phosphoproteins]

To cite this abstract in AMA style:

Nuñez Barrachina M, Hermida-Nogueira L, Morán LA, Casas V, Hicks SM, Sueiro AM, Din Y, Andrews RK, Gardiner EE, Abián J, Carrascal M, Pardo M, García Á. Phosphoproteomic Fingerprint of Platelets in Obesity: Insights into Platelet Reactivity [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/phosphoproteomic-fingerprint-of-platelets-in-obesity-insights-into-platelet-reactivity/. Accessed September 21, 2023.

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