PMID- 35932505 OWN - NLM STAT- MEDLINE DCOM- 20220830 LR - 20221006 IS - 1980-5322 (Electronic) IS - 1807-5932 (Print) IS - 1807-5932 (Linking) VI - 77 DP - 2022 TI - Resveratrol attenuates chronic pulmonary embolism-related endothelial cell injury by modulating oxidative stress, inflammation, and autophagy. PG - 100083 LID - S1807-5932(22)03284-7 [pii] LID - 10.1016/j.clinsp.2022.100083 [doi] LID - 100083 AB - 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. CI - Copyright (c) 2022. Published by Elsevier Espana, S.L.U. FAU - Liu, Xiaopeng AU - Liu X AD - Department of Respiratory Medicine, Jinshan Hospital Affiliated to Fudan University, Shanghai, China. FAU - Zhou, Haiying AU - Zhou H AD - Department of Respiratory Medicine, Jinshan Hospital Affiliated to Fudan University, Shanghai, China. FAU - Hu, Zhixiong AU - Hu Z AD - Department of Respiratory Medicine, Jinshan Hospital Affiliated to Fudan University, Shanghai, China. Electronic address: huzx321@sina.com. LA - eng PT - Journal Article DEP - 20220803 PL - United States TA - Clinics (Sao Paulo) JT - Clinics (Sao Paulo, Brazil) JID - 101244734 RN - EC 3.4.21.5 (Thrombin) RN - Q369O8926L (Resveratrol) SB - IM MH - Animals MH - Autophagy MH - Endothelial Cells MH - Humans MH - *Hypertension, Pulmonary MH - Inflammation MH - Oxidative Stress MH - Pulmonary Artery MH - *Pulmonary Embolism MH - Rats MH - Resveratrol MH - Thrombin PMC - PMC9357834 OTO - NOTNLM OT - Autophagy OT - Chronic thromboembolic pulmonary hypertension OT - Inflammation OT - Oxidative stress OT - Pulmonary artery endothelial dysfunction OT - Resveratrol COIS- Conflicts of interest The authors declare no conflicts of interest. EDAT- 2022/08/07 06:00 MHDA- 2022/08/31 06:00 PMCR- 2022/08/03 CRDT- 2022/08/06 18:14 PHST- 2021/12/16 00:00 [received] PHST- 2022/05/04 00:00 [accepted] PHST- 2022/08/07 06:00 [pubmed] PHST- 2022/08/31 06:00 [medline] PHST- 2022/08/06 18:14 [entrez] PHST- 2022/08/03 00:00 [pmc-release] AID - S1807-5932(22)03284-7 [pii] AID - 100083 [pii] AID - 10.1016/j.clinsp.2022.100083 [doi] PST - epublish SO - Clinics (Sao Paulo). 2022 Aug 3;77:100083. doi: 10.1016/j.clinsp.2022.100083. eCollection 2022.