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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doaj-5f291cbfe91f44818ff1c07e83765dcc2020-12-08T04:25:57ZengNature Publishing GroupScientific Reports2045-23222018-10-018111010.1038/s41598-018-33403-0Persistent platelet activation and apoptosis in virologically suppressed HIV-infected individualsEmersom C. Mesquita0Eugenio D. Hottz1Rodrigo T. Amancio2Alan B. Carneiro3Lohanna Palhinha4Lara E. Coelho5Beatriz Grinsztejn6Guy A. Zimmerman7Matthew T. Rondina8Andrew S. Weyrich9Patrícia T. Bozza10Fernando A. Bozza11Laboratório de Medicina Intensiva, Instituto Nacional de Infectologia Evandro Chagas (INI), Fundação Oswaldo Cruz (FIOCRUZ)Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz (IOC) – Fundação Oswaldo Cruz (FIOCRUZ)Laboratório de Medicina Intensiva, Instituto Nacional de Infectologia Evandro Chagas (INI), Fundação Oswaldo Cruz (FIOCRUZ)Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz (IOC) – Fundação Oswaldo Cruz (FIOCRUZ)Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz (IOC) – Fundação Oswaldo Cruz (FIOCRUZ)Laboratório de HIV, Instituto Nacional de Infectologia Evandro Chagas (INI), Fundação Oswaldo Cruz (FIOCRUZ)Laboratório de HIV, Instituto Nacional de Infectologia Evandro Chagas (INI), Fundação Oswaldo Cruz (FIOCRUZ)Molecular Medicine Program and Department of Internal Medicine, University of UtahMolecular Medicine Program and Department of Internal Medicine, University of UtahMolecular Medicine Program and Department of Internal Medicine, University of UtahLaboratório de Imunofarmacologia, Instituto Oswaldo Cruz (IOC) – Fundação Oswaldo Cruz (FIOCRUZ)Laboratório de Medicina Intensiva, Instituto Nacional de Infectologia Evandro Chagas (INI), Fundação Oswaldo Cruz (FIOCRUZ)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.https://doi.org/10.1038/s41598-018-33403-0Increased Platelet ActivationVirologic SuppressionRANTES SecretionStable cARTPlatelet Spreading |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
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 |
spellingShingle |
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 Scientific Reports Increased Platelet Activation Virologic Suppression RANTES Secretion Stable cART Platelet Spreading |
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 Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2018-10-01 |
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. |
topic |
Increased Platelet Activation Virologic Suppression RANTES Secretion Stable cART Platelet Spreading |
url |
https://doi.org/10.1038/s41598-018-33403-0 |
work_keys_str_mv |
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