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The integrin αIIbβ3 signalling pathway is hyperactivated in platelets from obese patients: a phosphoproteomic study
ISTH Academy. Nuñez Barrachina M. Jul 9, 2019; 264741; PB1552
Mrs. Maria Nuñez Barrachina
Mrs. Maria Nuñez Barrachina
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PB1552

The Integrin αIIbβ3 Signalling Pathway is Hyperactivated in Platelets from Obese Patients: A Phosphoproteomic Study

M. N. Barrachina1,2, I. Izquierdo1,2, L. Hermida-Nogueira1,2, L. Moran1,2, A. M. Sueiro3,4, V. Casas5, A. Casanovas5, F. F. Casanueva3, J. Abián5, M. Carrascal5, M. Pardo6, Á. García1,2
1University of Santiago de Compostela, Platelet Proteomics, Santiago de Compostela, Spain, 2Instituto de Investigación Sanitaria de Santiago, Santiago de Compostela, Spain, 3Instituto de Investigación Sanitaria de Santiago, Grupo de Endocrinología Molecular y Celular, Santiago de Compostela, Spain, 4Xerencia de Xestión Integrada de Santiago, Servicio de Endocrinología, Santiago de Compostela, Spain, 5IIBB-CSIC-IDIBAPS, CSIC/UAB Proteomics Laboratory, Barcelona, Spain, 6Instituto de Investigación Sanitaria de Santiago, Grupo Obesidómica, Santiago de Compostela, Spain

Main Topic: Platelets and Megakaryocytes
Category: Platelet Proteomics & Genomics

Background: Platelets play a fundamental role in the increased atherothrombotic risk related to obesity since they show hyperactivation and lower sensitivity to antiplatelet therapy.
Aims: The aim of this study was to identify potential biomarkers and altered activation pathways associated to the risk of suffering atherothrombosis in obesity.
Methods: We performed a comparative phosphoproteomic analysis of platelets from obese patients and their age- and sex-matched controls. Platelets were obtained from a cohort of 24 individuals (12 obese patients and 12 lean controls). Phosphopeptides were enriched with TiO2 and analyzed by mass spectrometry. Differential analysis was done by Progenesis QI software. Moreover, we also analyzed the surface expression of integrin αIIbβ3 by flow cytometry in an independent cohort of patients.
Results: Regarding the proteomic analysis, we identified 224 differentially regulated phosphopeptides; interestingly all of them were up-regulated in obesity. These phosphopeptides described at least 183 proteins; most of them related to platelet activation, vesicle transport and cytoskeleton organization. One of the altered pathways identified was integrin αIIbβ3 signalling, which plays an important role in platelet activation. Our results show an up-regulation of key phosphosites from relevant proteins of the signalling cascade. Among others, integrin β3 tail (Thr788) is increased in obesity, which is necessary for Src-kinase family (SFKs) binding upon activation. Indeed, we also found increased SFKs Tyr419 residue, which supports the kinase full activation. Other phosphoproteins up-regulated in obesity are involved in integrin downstream signalling such as PKCθ (S695) and Filamin-1 (S1459), which support calcium liberation and cytoskeleton reorganization. In line with the above, we also found higher surface expression levels of integrin αIIbβ3 in obese patients confirming a potential activation of the pathway.
Conclusions: In summary, our results show an up-regulation of the αIIbβ3 signalling pathway in platelets from obese patients, which could be essential to further understand platelet hyperactivation in obesity.

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