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Temporal in vivo platelet labeling in mice reveals age-dependent receptor expression and conservation of specific mRNAs

The proportion of young platelets, also known as newly formed or reticulated, within the overall platelet population has been clinically correlated with adverse cardiovascular outcomes. However, our understanding of this is incomplete because of limitations in the technical approaches available to s...

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Autores principales: Armstrong, Paul C., Allan, Harriet E., Kirkby, Nicholas S., Gutmann, Clemens, Joshi, Abhishek, Crescente, Marilena, Mitchell, Jane A., Mayr, Manuel, Warner, Timothy D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society of Hematology 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9699941/
https://www.ncbi.nlm.nih.gov/pubmed/36037520
http://dx.doi.org/10.1182/bloodadvances.2022007099
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author Armstrong, Paul C.
Allan, Harriet E.
Kirkby, Nicholas S.
Gutmann, Clemens
Joshi, Abhishek
Crescente, Marilena
Mitchell, Jane A.
Mayr, Manuel
Warner, Timothy D.
author_facet Armstrong, Paul C.
Allan, Harriet E.
Kirkby, Nicholas S.
Gutmann, Clemens
Joshi, Abhishek
Crescente, Marilena
Mitchell, Jane A.
Mayr, Manuel
Warner, Timothy D.
author_sort Armstrong, Paul C.
collection PubMed
description The proportion of young platelets, also known as newly formed or reticulated, within the overall platelet population has been clinically correlated with adverse cardiovascular outcomes. However, our understanding of this is incomplete because of limitations in the technical approaches available to study platelets of different ages. In this study, we have developed and validated an in vivo temporal labeling approach using injectable fluorescent antiplatelet antibodies to subdivide platelets by age and assess differences in functional and molecular characteristics. With this approach, we found that young platelets (<24 hours old) in comparison with older platelets respond to stimuli with greater calcium flux and degranulation and contribute more to the formation of thrombi in vitro and in vivo. Sequential sampling confirmed this altered functionality to be independent of platelet size, with distribution of sizes of tracked platelets commensurate with the global platelet population throughout their 5-day lifespan in the circulation. The age-associated decrease in thrombotic function was accompanied by significant decreases in the surface expression of GPVI and CD31 (PECAM-1) and an increase in CD9. Platelet messenger RNA (mRNA) content also decreased with age but at different rates for individual mRNAs indicating apparent conservation of those encoding granule proteins. Our pulse-chase–type approach to define circulating platelet age has allowed timely reexamination of commonly held beliefs regarding size and reactivity of young platelets while providing novel insights into the temporal regulation of receptor and protein expression. Overall, future application of this validated tool will inform age-based platelet heterogeneity in physiology and disease.
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spelling pubmed-96999412022-11-30 Temporal in vivo platelet labeling in mice reveals age-dependent receptor expression and conservation of specific mRNAs Armstrong, Paul C. Allan, Harriet E. Kirkby, Nicholas S. Gutmann, Clemens Joshi, Abhishek Crescente, Marilena Mitchell, Jane A. Mayr, Manuel Warner, Timothy D. Blood Adv Regular Article The proportion of young platelets, also known as newly formed or reticulated, within the overall platelet population has been clinically correlated with adverse cardiovascular outcomes. However, our understanding of this is incomplete because of limitations in the technical approaches available to study platelets of different ages. In this study, we have developed and validated an in vivo temporal labeling approach using injectable fluorescent antiplatelet antibodies to subdivide platelets by age and assess differences in functional and molecular characteristics. With this approach, we found that young platelets (<24 hours old) in comparison with older platelets respond to stimuli with greater calcium flux and degranulation and contribute more to the formation of thrombi in vitro and in vivo. Sequential sampling confirmed this altered functionality to be independent of platelet size, with distribution of sizes of tracked platelets commensurate with the global platelet population throughout their 5-day lifespan in the circulation. The age-associated decrease in thrombotic function was accompanied by significant decreases in the surface expression of GPVI and CD31 (PECAM-1) and an increase in CD9. Platelet messenger RNA (mRNA) content also decreased with age but at different rates for individual mRNAs indicating apparent conservation of those encoding granule proteins. Our pulse-chase–type approach to define circulating platelet age has allowed timely reexamination of commonly held beliefs regarding size and reactivity of young platelets while providing novel insights into the temporal regulation of receptor and protein expression. Overall, future application of this validated tool will inform age-based platelet heterogeneity in physiology and disease. The American Society of Hematology 2022-08-30 /pmc/articles/PMC9699941/ /pubmed/36037520 http://dx.doi.org/10.1182/bloodadvances.2022007099 Text en © 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Regular Article
Armstrong, Paul C.
Allan, Harriet E.
Kirkby, Nicholas S.
Gutmann, Clemens
Joshi, Abhishek
Crescente, Marilena
Mitchell, Jane A.
Mayr, Manuel
Warner, Timothy D.
Temporal in vivo platelet labeling in mice reveals age-dependent receptor expression and conservation of specific mRNAs
title Temporal in vivo platelet labeling in mice reveals age-dependent receptor expression and conservation of specific mRNAs
title_full Temporal in vivo platelet labeling in mice reveals age-dependent receptor expression and conservation of specific mRNAs
title_fullStr Temporal in vivo platelet labeling in mice reveals age-dependent receptor expression and conservation of specific mRNAs
title_full_unstemmed Temporal in vivo platelet labeling in mice reveals age-dependent receptor expression and conservation of specific mRNAs
title_short Temporal in vivo platelet labeling in mice reveals age-dependent receptor expression and conservation of specific mRNAs
title_sort temporal in vivo platelet labeling in mice reveals age-dependent receptor expression and conservation of specific mrnas
topic Regular Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9699941/
https://www.ncbi.nlm.nih.gov/pubmed/36037520
http://dx.doi.org/10.1182/bloodadvances.2022007099
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