Resveratrol attenuates chronic pulmonary embolism-related endothelial cell injury by modulating oxidative stress, inflammation, and autophagy
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Clinics |
Texto Completo: | https://www.revistas.usp.br/clinics/article/view/213531 |
Resumo: | Objectives: Due to Pulmonary Artery Endothelial Cell (PAEC) dysfunction, Pulmonary Hypertension (PH) persists even after the Pulmonary Embolism (PE) has been relieved. However, the mechanism behind this remains unclear. Method: Here, the authors incubated Human PAECs (HPAECs) with thrombin to simulate the process of arterial thrombosis. Results: CCK8 results showed a decrease in the viability of HPAECs after thrombin incubation. In addition, the expression of Tissue Factor (TF), Monocyte Chemoattractant Protein 1 (MCP-1), VCAM-1, ICAM-1, cleaved caspase 3, cleaved caspase 9, and Bax protein were all increased after thrombin incubation, while Bcl-2 was decreased. The effects of 3-MA treatment further suggested that autophagy might mediate the partial protective effects of Resveratrol on HPAECs. To observe the effects of Resveratrol in vivo, the authors established a Chronic Thromboembolic Pulmonary Hypertension (CTEPH) model by repeatedly injecting autologous blood clots into a rat's left jugular vein. The results exhibited that Mean Pulmonary Arterial Pressure (mPAP) and vessel Wall Area/Total Area (WA/TA) ratio were both decreased after Resveratrol treatment. Moreover, Resveratrol could reduce the concentration and activity of TF, vWF, P-selectin, and promote these Superoxide Dismutase (SOD) in plasma. Western blot analysis of inflammation, platelet activation, autophagy, and apoptosis-associated proteins in pulmonary artery tissue validated the results in PHAECs. Conclusions: These findings suggested that reduced autophagy, increased oxidative stress, increased platelet activation, and increased inflammation were involved in CTEPH-induced HPAEC dysfunction and the development of PH, while Resveratrol could improve PAEC dysfunction and PH. |
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Clinics |
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Resveratrol attenuates chronic pulmonary embolism-related endothelial cell injury by modulating oxidative stress, inflammation, and autophagyPulmonary artery endothelial dysfunctionChronic thromboembolic pulmonary hypertensionOxidative stressInflammationAutophagyResveratrolObjectives: Due to Pulmonary Artery Endothelial Cell (PAEC) dysfunction, Pulmonary Hypertension (PH) persists even after the Pulmonary Embolism (PE) has been relieved. However, the mechanism behind this remains unclear. Method: Here, the authors incubated Human PAECs (HPAECs) with thrombin to simulate the process of arterial thrombosis. Results: CCK8 results showed a decrease in the viability of HPAECs after thrombin incubation. In addition, the expression of Tissue Factor (TF), Monocyte Chemoattractant Protein 1 (MCP-1), VCAM-1, ICAM-1, cleaved caspase 3, cleaved caspase 9, and Bax protein were all increased after thrombin incubation, while Bcl-2 was decreased. The effects of 3-MA treatment further suggested that autophagy might mediate the partial protective effects of Resveratrol on HPAECs. To observe the effects of Resveratrol in vivo, the authors established a Chronic Thromboembolic Pulmonary Hypertension (CTEPH) model by repeatedly injecting autologous blood clots into a rat's left jugular vein. The results exhibited that Mean Pulmonary Arterial Pressure (mPAP) and vessel Wall Area/Total Area (WA/TA) ratio were both decreased after Resveratrol treatment. Moreover, Resveratrol could reduce the concentration and activity of TF, vWF, P-selectin, and promote these Superoxide Dismutase (SOD) in plasma. Western blot analysis of inflammation, platelet activation, autophagy, and apoptosis-associated proteins in pulmonary artery tissue validated the results in PHAECs. Conclusions: These findings suggested that reduced autophagy, increased oxidative stress, increased platelet activation, and increased inflammation were involved in CTEPH-induced HPAEC dysfunction and the development of PH, while Resveratrol could improve PAEC dysfunction and PH.Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo2022-08-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://www.revistas.usp.br/clinics/article/view/21353110.1016/j.clinsp.2022.100083Clinics; Vol. 77 (2022); 100083Clinics; v. 77 (2022); 100083Clinics; Vol. 77 (2022); 1000831980-53221807-5932reponame:Clinicsinstname:Universidade de São Paulo (USP)instacron:USPenghttps://www.revistas.usp.br/clinics/article/view/213531/195622Copyright (c) 2023 Clinicsinfo:eu-repo/semantics/openAccessLiu, XiaopengZhou, HaiyingHu, Zhixiong2023-07-06T13:04:58Zoai:revistas.usp.br:article/213531Revistahttps://www.revistas.usp.br/clinicsPUBhttps://www.revistas.usp.br/clinics/oai||clinics@hc.fm.usp.br1980-53221807-5932opendoar:2023-07-06T13:04:58Clinics - Universidade de São Paulo (USP)false |
dc.title.none.fl_str_mv |
Resveratrol attenuates chronic pulmonary embolism-related endothelial cell injury by modulating oxidative stress, inflammation, and autophagy |
title |
Resveratrol attenuates chronic pulmonary embolism-related endothelial cell injury by modulating oxidative stress, inflammation, and autophagy |
spellingShingle |
Resveratrol attenuates chronic pulmonary embolism-related endothelial cell injury by modulating oxidative stress, inflammation, and autophagy Liu, Xiaopeng Pulmonary artery endothelial dysfunction Chronic thromboembolic pulmonary hypertension Oxidative stress Inflammation Autophagy Resveratrol |
title_short |
Resveratrol attenuates chronic pulmonary embolism-related endothelial cell injury by modulating oxidative stress, inflammation, and autophagy |
title_full |
Resveratrol attenuates chronic pulmonary embolism-related endothelial cell injury by modulating oxidative stress, inflammation, and autophagy |
title_fullStr |
Resveratrol attenuates chronic pulmonary embolism-related endothelial cell injury by modulating oxidative stress, inflammation, and autophagy |
title_full_unstemmed |
Resveratrol attenuates chronic pulmonary embolism-related endothelial cell injury by modulating oxidative stress, inflammation, and autophagy |
title_sort |
Resveratrol attenuates chronic pulmonary embolism-related endothelial cell injury by modulating oxidative stress, inflammation, and autophagy |
author |
Liu, Xiaopeng |
author_facet |
Liu, Xiaopeng Zhou, Haiying Hu, Zhixiong |
author_role |
author |
author2 |
Zhou, Haiying Hu, Zhixiong |
author2_role |
author author |
dc.contributor.author.fl_str_mv |
Liu, Xiaopeng Zhou, Haiying Hu, Zhixiong |
dc.subject.por.fl_str_mv |
Pulmonary artery endothelial dysfunction Chronic thromboembolic pulmonary hypertension Oxidative stress Inflammation Autophagy Resveratrol |
topic |
Pulmonary artery endothelial dysfunction Chronic thromboembolic pulmonary hypertension Oxidative stress Inflammation Autophagy Resveratrol |
description |
Objectives: Due to Pulmonary Artery Endothelial Cell (PAEC) dysfunction, Pulmonary Hypertension (PH) persists even after the Pulmonary Embolism (PE) has been relieved. However, the mechanism behind this remains unclear. Method: Here, the authors incubated Human PAECs (HPAECs) with thrombin to simulate the process of arterial thrombosis. Results: CCK8 results showed a decrease in the viability of HPAECs after thrombin incubation. In addition, the expression of Tissue Factor (TF), Monocyte Chemoattractant Protein 1 (MCP-1), VCAM-1, ICAM-1, cleaved caspase 3, cleaved caspase 9, and Bax protein were all increased after thrombin incubation, while Bcl-2 was decreased. The effects of 3-MA treatment further suggested that autophagy might mediate the partial protective effects of Resveratrol on HPAECs. To observe the effects of Resveratrol in vivo, the authors established a Chronic Thromboembolic Pulmonary Hypertension (CTEPH) model by repeatedly injecting autologous blood clots into a rat's left jugular vein. The results exhibited that Mean Pulmonary Arterial Pressure (mPAP) and vessel Wall Area/Total Area (WA/TA) ratio were both decreased after Resveratrol treatment. Moreover, Resveratrol could reduce the concentration and activity of TF, vWF, P-selectin, and promote these Superoxide Dismutase (SOD) in plasma. Western blot analysis of inflammation, platelet activation, autophagy, and apoptosis-associated proteins in pulmonary artery tissue validated the results in PHAECs. Conclusions: These findings suggested that reduced autophagy, increased oxidative stress, increased platelet activation, and increased inflammation were involved in CTEPH-induced HPAEC dysfunction and the development of PH, while Resveratrol could improve PAEC dysfunction and PH. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-08-03 |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://www.revistas.usp.br/clinics/article/view/213531 10.1016/j.clinsp.2022.100083 |
url |
https://www.revistas.usp.br/clinics/article/view/213531 |
identifier_str_mv |
10.1016/j.clinsp.2022.100083 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
https://www.revistas.usp.br/clinics/article/view/213531/195622 |
dc.rights.driver.fl_str_mv |
Copyright (c) 2023 Clinics info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Copyright (c) 2023 Clinics |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo |
publisher.none.fl_str_mv |
Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo |
dc.source.none.fl_str_mv |
Clinics; Vol. 77 (2022); 100083 Clinics; v. 77 (2022); 100083 Clinics; Vol. 77 (2022); 100083 1980-5322 1807-5932 reponame:Clinics instname:Universidade de São Paulo (USP) instacron:USP |
instname_str |
Universidade de São Paulo (USP) |
instacron_str |
USP |
institution |
USP |
reponame_str |
Clinics |
collection |
Clinics |
repository.name.fl_str_mv |
Clinics - Universidade de São Paulo (USP) |
repository.mail.fl_str_mv |
||clinics@hc.fm.usp.br |
_version_ |
1800222766672117760 |