Overexpression of PRDX2 alleviates chronic thromboembolic pulmonary hypertension by modulating inflammation and mitophagy

Abstract

Chronic thromboembolic pulmonary hypertension (CTEPH) results from thrombi-induced endothelial injury, inflammation, and oxidative stress in pulmonary vessels, leading to vascular remodelling, increased resistance, and elevated pulmonary arterial pressure. Peroxiredoxin 2 (PRDX2) is an antioxidant enzyme involved in regulating cellular redox balance and inflammation, its role in CTEPH is not yet fully understood. The aim is to investigate the expression and functional role of PRDX2 in CTEPH and explore its potential mechanisms in modulating inflammation and mitochondrial autophagy. Proteomics was used to analyse peripheral blood samples from patients with CTEPH and healthy controls to identify differentially expressed proteins. A rat model of CTEPH was developed through the intravenous injection of amino-crosslinked polystyrene microspheres. PRDX2 expression was assessed in lung tissues and primary pulmonary artery endothelial cells (PAECs) using immunohistochemistry, Western blotting, and qRT-PCR. The effects of PRDX2 overexpression and silencing on inflammation and mitochondrial autophagy were evaluated using ELISA, Western blotting, and transmission electron microscopy. The expression of PRDX2 was significantly increased in the peripheral blood of patients with CTEPH and in the pulmonary vasculature of rats with CTEPH.Overexpression of PRDX2 in PAECs attenuated the inflammatory response by NF-κB signaling pathway. Additionally, overexpression of PRDX2 regulated the expression of mitophagy-related proteins (LC3II/I, Beclin-1, and p62) and restored mitochondrial morphology. Further verification in rats showed that PRDX2 overexpression significantly improved haemodynamic parameters and pulmonary vascular remodelling in CTEPH. Overexpression of PRDX2 alleviates pulmonary vascular remodeling in CTEPH by reducing inflammation and Modulating mitophagy, suggesting its protective role and potential as a therapeutic target for the disease.

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Affiliated Institutions

• Guangxi University of Chinese Medicine CN
• First Affiliated Hospital of GuangXi Medical University CN
• Guangxi Center for Disease Prevention and Control CN
• Guangxi Medical University CN

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