Persistent platelet activation and apoptosis in virologically suppressed HIV-infected individuals

Abstract Cardiovascular diseases and thrombotic events became major clinical problems in the combined antiretroviral therapy (cART) era. Although the precise mechanisms behind these clinical problems have not been fully elucidated, a persistent pro-inflammatory state plays a central role. As platele...

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Autores principales:	Emersom C. Mesquita, Eugenio D. Hottz, Rodrigo T. Amancio, Alan B. Carneiro, Lohanna Palhinha, Lara E. Coelho, Beatriz Grinsztejn, Guy A. Zimmerman, Matthew T. Rondina, Andrew S. Weyrich, Patrícia T. Bozza, Fernando A. Bozza
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Increased Platelet Activation Virologic Suppression RANTES Secretion Stable cART Platelet Spreading Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5f291cbfe91f44818ff1c07e83765dcc
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spelling	oai:doaj.org-article:5f291cbfe91f44818ff1c07e83765dcc2021-12-02T15:07:58ZPersistent platelet activation and apoptosis in virologically suppressed HIV-infected individuals10.1038/s41598-018-33403-02045-2322https://doaj.org/article/5f291cbfe91f44818ff1c07e83765dcc2018-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-33403-0https://doaj.org/toc/2045-2322Abstract Cardiovascular diseases and thrombotic events became major clinical problems in the combined antiretroviral therapy (cART) era. Although the precise mechanisms behind these clinical problems have not been fully elucidated, a persistent pro-inflammatory state plays a central role. As platelets play important roles on both, thrombus formation and inflammatory/immune response, we aimed at investigating platelet function in HIV-infected subjects virologically controlled through cART. We evaluate parameters of activation, mitochondrial function and activation of apoptosis pathways in platelets from 30 HIV-infected individuals under stable cART and 36 healthy volunteers. Despite viral control achieved through cART, HIV-infected individuals exhibited increased platelet activation as indicated by P-selectin expression and platelet spreading when adhered on fibrinogen-coated surfaces. Platelets from HIV-infected subjects also exhibited mitochondrial dysfunction and activation of apoptosis pathways. Finally, thrombin stimuli induced lower levels of P-selectin translocation and RANTES secretion, but not TXA2 synthesis, in platelets from HIV-infected individuals compared to control; and labeling of platelet alpha granules showed reduced granule content in platelets from HIV-infected individuals when compared to healthy subjects. In summary, platelets derived from HIV-infected individuals under stable cART exhibit a phenotype of increased activation, activation of the intrinsic pathway of apoptosis and undermined granule secretion in response to thrombin.Emersom C. MesquitaEugenio D. HottzRodrigo T. AmancioAlan B. CarneiroLohanna PalhinhaLara E. CoelhoBeatriz GrinsztejnGuy A. ZimmermanMatthew T. RondinaAndrew S. WeyrichPatrícia T. BozzaFernando A. BozzaNature PortfolioarticleIncreased Platelet ActivationVirologic SuppressionRANTES SecretionStable cARTPlatelet SpreadingMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-10 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Increased Platelet Activation Virologic Suppression RANTES Secretion Stable cART Platelet Spreading Medicine R Science Q
spellingShingle	Increased Platelet Activation Virologic Suppression RANTES Secretion Stable cART Platelet Spreading Medicine R Science Q Emersom C. Mesquita Eugenio D. Hottz Rodrigo T. Amancio Alan B. Carneiro Lohanna Palhinha Lara E. Coelho Beatriz Grinsztejn Guy A. Zimmerman Matthew T. Rondina Andrew S. Weyrich Patrícia T. Bozza Fernando A. Bozza Persistent platelet activation and apoptosis in virologically suppressed HIV-infected individuals
description	Abstract Cardiovascular diseases and thrombotic events became major clinical problems in the combined antiretroviral therapy (cART) era. Although the precise mechanisms behind these clinical problems have not been fully elucidated, a persistent pro-inflammatory state plays a central role. As platelets play important roles on both, thrombus formation and inflammatory/immune response, we aimed at investigating platelet function in HIV-infected subjects virologically controlled through cART. We evaluate parameters of activation, mitochondrial function and activation of apoptosis pathways in platelets from 30 HIV-infected individuals under stable cART and 36 healthy volunteers. Despite viral control achieved through cART, HIV-infected individuals exhibited increased platelet activation as indicated by P-selectin expression and platelet spreading when adhered on fibrinogen-coated surfaces. Platelets from HIV-infected subjects also exhibited mitochondrial dysfunction and activation of apoptosis pathways. Finally, thrombin stimuli induced lower levels of P-selectin translocation and RANTES secretion, but not TXA2 synthesis, in platelets from HIV-infected individuals compared to control; and labeling of platelet alpha granules showed reduced granule content in platelets from HIV-infected individuals when compared to healthy subjects. In summary, platelets derived from HIV-infected individuals under stable cART exhibit a phenotype of increased activation, activation of the intrinsic pathway of apoptosis and undermined granule secretion in response to thrombin.
format	article
author	Emersom C. Mesquita Eugenio D. Hottz Rodrigo T. Amancio Alan B. Carneiro Lohanna Palhinha Lara E. Coelho Beatriz Grinsztejn Guy A. Zimmerman Matthew T. Rondina Andrew S. Weyrich Patrícia T. Bozza Fernando A. Bozza
author_facet	Emersom C. Mesquita Eugenio D. Hottz Rodrigo T. Amancio Alan B. Carneiro Lohanna Palhinha Lara E. Coelho Beatriz Grinsztejn Guy A. Zimmerman Matthew T. Rondina Andrew S. Weyrich Patrícia T. Bozza Fernando A. Bozza
author_sort	Emersom C. Mesquita
title	Persistent platelet activation and apoptosis in virologically suppressed HIV-infected individuals
title_short	Persistent platelet activation and apoptosis in virologically suppressed HIV-infected individuals
title_full	Persistent platelet activation and apoptosis in virologically suppressed HIV-infected individuals
title_fullStr	Persistent platelet activation and apoptosis in virologically suppressed HIV-infected individuals
title_full_unstemmed	Persistent platelet activation and apoptosis in virologically suppressed HIV-infected individuals
title_sort	persistent platelet activation and apoptosis in virologically suppressed hiv-infected individuals
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/5f291cbfe91f44818ff1c07e83765dcc
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Persistent platelet activation and apoptosis in virologically suppressed HIV-infected individuals

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