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Proteome and functional decline as platelets age in the circulation

Research output: Contribution to journalArticlepeer-review

Harriet E. Allan, Melissa A. Hayman, Simone Marcone, Melissa V. Chan, Matthew L. Edin, Tania Maffucci, Abhishek Joshi, Laura Menke, Marilena Crescente, Manuel Mayr, Darryl C. Zeldin, Paul C. Armstrong, Timothy D. Warner

Original languageEnglish
Pages (from-to)3095-3112
Number of pages18
JournalJournal of Thrombosis and Haemostasis
Volume19
Issue number12
Early online date27 Aug 2021
DOIs
Accepted/In press2021
E-pub ahead of print27 Aug 2021
PublishedDec 2021

Bibliographical note

Funding Information: Funding for this project was provided by Barts & the London School of Medicine and Dentistry, Queen Mary University of London; the British Heart Foundation (PG/15/47/31591, PG/17/40/33028, RG/19/8/34500); the Division of Intramural Research, National Institute of Environmental Health Sciences, NIH (Z01 ES025034 to D.C.Z.), the Wellcome Trust (101604/Z/13/Z) and the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska‐Curie grant agreement No 675111. Funding Information: Funding for this project was provided by Barts & the London School of Medicine and Dentistry, Queen Mary University of London; the British Heart Foundation (PG/15/47/31591, PG/17/40/33028, RG/19/8/34500); the Division of Intramural Research, National Institute of Environmental Health Sciences, NIH (Z01 ES025034 to D.C.Z.), the Wellcome Trust (101604/Z/13/Z) and the European Union's Horizon 2020 research and innovation programme under the Marie Sk?odowska-Curie grant agreement No 675111. The authors acknowledge the support the Flow Cytometry Core Facilities at the Blizard Institute and Charterhouse Square, Queen Mary University of London and the UCD Conway Institute mass spectrometry facilities. Publisher Copyright: © 2021 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis.

King's Authors

Abstract

Background: Platelets circulate in the blood of healthy individuals for approximately 7–10 days regulated by finely balanced processes of production and destruction. As platelets are anucleate we reasoned that their protein composition would change as they age and that this change would be linked to alterations in structure and function. Objective: To isolate platelets of different ages from healthy individuals to test the hypothesis that changes in protein content cause alterations in platelet structure and function. Methods: Platelets were separated according to thiazole orange fluorescence intensity as a surrogate indicator of mRNA content and so a marker of platelet age and then subjected to proteomics, imaging, and functional assays to produce an in-depth analysis of platelet composition and function. Results: Total protein content was 45 ± 5% lower in old platelets compared to young platelets. Predictive proteomic pathway analysis identified associations with 28 biological processes, notably higher hemostasis in young platelets whilst apoptosis and senescence were higher in old platelets. Further studies confirmed platelet ageing was linked to a decrease in cytoskeletal protein and associated capability to spread and adhere, a reduction in mitochondria number, and lower calcium dynamics and granule secretion. Conclusions: Our findings demonstrate changes in protein content are linked to alterations in function as platelets age. This work delineates physical and functional changes in platelets as they age and serves as a base to examine differences associated with altered mean age of platelet populations in conditions such as immune thrombocytopenia and diabetes.

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