eIF2α promotes vascular remodeling via autophagy in monocrotaline-induced pulmonary arterial hypertension rats
Autor: | Ying Tian, Xi Chen, Tianhong Peng, Zhisheng Jiang, Linya Guo, Shao-Xin Gong, Aiping Wang, Yanbing Li |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Platelet-derived growth factor Pharmaceutical Science 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Downregulation and upregulation Eukaryotic initiation factor medicine.artery Drug Discovery medicine Pharmacology biology business.industry Autophagy medicine.disease Pulmonary hypertension In vitro 030104 developmental biology chemistry 030220 oncology & carcinogenesis Pulmonary artery biology.protein Cancer research business Platelet-derived growth factor receptor |
Zdroj: | Drug Design, Development and Therapy. 13:2799-2809 |
ISSN: | 1177-8881 |
Popis: | Purpose Eukaryotic initiation factor 2α (eIF2α) plays important roles in the proliferation and survival of pulmonary artery smooth muscle cells (PASMCs) in animal hypoxia-induced pulmonary hypertension models. However, the underlying mechanism remains unknown at large. Autophagy has been reported to play a key role in the vascular remodeling in pulmonary arterial hypertension (PAH). The purposes of this study are to determine the functions of eIF2α and autophagy in the vascular remodeling of the monocrotaline-induced PAH rats and to clarify the correlation between eIF2α and autophagy. Methods We established a rat model of monocrotaline-induced PAH, and we established a cell model of platelet derived growth factor (PDGF)-induced PASMCs proliferation. The vascular morphology and the expression of eIF2α, LC3B, and p62 were assessed in the pulmonary arterial tissue of Sprague-Dawleyrats and PDGF-induced PASMCs. Results Autophagy was significantly active in monocrotaline model group (MCT)-induced PAH rats, which obviously promotes vascular remodeling in MCT-induced PAH rats. Furthermore, the proliferation of PASMCs was induced by PDGF in vitro. The expression of LC3B, eIF2α was increased in the PDGF-induced PASMCs proliferation, and the expression of p62 was reduced in the PDGF-induced PASMCs proliferation. Moreover, eIF2α siRNA downregulated the expression of eIF2α and LC3B, and upregulated the expression of p62 in PDGF-induced PASMCs proliferation. eIF2α siRNA inhibited the PDGF-induced PASMCs proliferation. Finally, chloroquine can upregulate the protein expression of LC3B and p62, it also can inhibit proliferation in PDGF-induced PASMCs. Conclusion Based on these observations, we conclude that eIF2α promotes the proliferation of PASMCs and vascular remodeling in monocrotaline-induced PAH rats through accelerating autophagy pathway. |
Databáze: | OpenAIRE |
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