Upregulation of eIF2α by m 6 A modification accelerates the proliferation of pulmonary artery smooth muscle cells in MCT-induced pulmonary arterial hypertension rats.

Autor: Zhang J; Department of Physiology, Institute of Neuroscience Research, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, People's Republic of China., Huang WQ; Department of Physiology, Institute of Neuroscience Research, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, People's Republic of China.; Institute of Clinical Research, Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, 421002, Hunan, People's Republic of China.; Department of Blood Transfusion, the First Affiliated of Hainan Medical University, Haikou, 570102, Hainan, People's Republic of China., Zhang YR; Department of Physiology, Institute of Neuroscience Research, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, People's Republic of China., Liang N; Department of Anesthesiology, Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, 421002, Hunan, People's Republic of China., Li NP; Department of Physiology, Institute of Neuroscience Research, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, People's Republic of China.; Department of Anesthesiology, Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, 421002, Hunan, People's Republic of China., Tan GK; Department of Physiology, Institute of Neuroscience Research, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, People's Republic of China.; Department of Anesthesiology, Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, 421002, Hunan, People's Republic of China., Gong SX; Department of Pathology, First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, People's Republic of China. 553648247@qq.com., Wang AP; Department of Physiology, Institute of Neuroscience Research, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, People's Republic of China. waiping2011@163.com.; Institute of Clinical Research, Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, 421002, Hunan, People's Republic of China. waiping2011@163.com.
Jazyk: angličtina
Zdroj: Journal of cardiovascular translational research [J Cardiovasc Transl Res] 2024 Jun; Vol. 17 (3), pp. 598-608. Date of Electronic Publication: 2023 Nov 16.
DOI: 10.1007/s12265-023-10458-7
Abstrakt: Pulmonary arterial hypertension (PAH) is a malignant cardiovascular disease. Eukaryotic initiation factor 2α (eIF2α) plays an important role in the proliferation of pulmonary artery smooth muscle cells (PASMCs) in hypoxia-induced pulmonary hypertension (HPH) rats. However, the regulatory mechanism of eIF2α remains poorly understood in PAH rats. Here, we discover eIF2α is markedly upregulated in monocrotaline (MCT)-induced PAH rats, eIF2α can be upregulated by mRNA methylation, and upregulated eIF2α can promote PASMC proliferation in MCT-PAH rats. GSK2606414, eIF2α inhibitor, can downregulate the expression of eIF2α and alleviate PASMC proliferation in MCT-PAH rats. And we further discover the mRNA of eIF2α has a common sequence with N 6-methyladenosine (m 6 A) modification by bioinformatics analysis, and the expression of METTL3, WTAP, and YTHDF1 is upregulated in MCT-PAH rats. These findings suggest a potentially novel mechanism by which eIF2α is upregulated by m 6 A modification in MCT-PAH rats, which is involved in the pathogenesis of PAH.
(© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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