Resveratrol attenuates chronic pulmonary embolism-related endothelial cell injury by modulating oxidative stress, inflammation, and autophagy

Abstract

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 cas-pase 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.

Keywords:
Pulmonary artery endothelial dysfunction; Chronic thromboembolic pulmonary; hypertension; Oxidative stress; Inflammation; Autophagy; Resveratrol

Highlights

• Resveratrol can effectively improve pulmonary thromboembolism-induced PAEC injury.

• Resveratrol can reduce pulmonary arterial pressure through a variety of mechanisms.

• These findings may contribute to the treatment of PH in the future.