Overexpressed microRNA (miR)-382-3p promoted vascular remodeling via suppressing autophagy-related protein 7 (ATG7) in chronic thromboembolic pulmonary hypertension

Xiaona Feng; Kaifeng Wang; Ting Yang; Bo Dang; Xiaodong Wang

doi:10.2174/1566524023666230822120453

Overexpressed microRNA (miR)-382-3p promoted vascular remodeling via suppressing autophagy-related protein 7 (ATG7) in chronic thromboembolic pulmonary hypertension

Curr Mol Med. 2023 Aug 22. doi: 10.2174/1566524023666230822120453. Online ahead of print.

Authors

Xiaona Feng¹, Kaifeng Wang², Ting Yang², Bo Dang², Xiaodong Wang²

Affiliations

¹ Department of Obstetrics and Gynecology, First Affiliated Hospital of Jiamusi University, No. 348, Dexiang Street, Xiangyang District, Jiamusi City, Heilongjiang Province, 154002, China.
² Vascular surgery, First Affiliated Hospital of Jiamusi University, No. 348, Dexiang Street, Xiangyang District, Jiamusi City, Heilongjiang Province, 154002, China.

PMID: 37608664
DOI: 10.2174/1566524023666230822120453

Abstract

Background: This research has investigated the role of miR-382-3p in chronic thromboembolic pulmonary hypertension (CTEPH).

Methods: Human pulmonary artery smooth muscle cells (hPASMCs) were treated with PDGF-BB to induce proliferation, and then transfected with miR-382-3p mimic, miR-382-3p inhibitor, ATG7 overexpression plasmid, and siATG7. MiR-382-3p, ATG7, VEGF, PCNA, p62, and LC3-Ⅱ/LC3-I levels were detected by qRT-PCR and Western blotting. Cell viability and migration were tested through CCK-8 and wound healing assays, respectively. Target genes of miR-382-3p were predicted by Targetscan and starBase, and pathway analysis was implemented through WebGestalt. The binding relationship between miR-382-3p and ATG7 was analyzed by the dual-luciferase reporter and RIP assays. A CTEPH model was constructed in rats with the treatment of miR-382-3p antagomir or agomir, and mean pulmonary artery pressure (mPAP) was measured. Lung tissue was observed through the HE staining assay.

Results: MiR-382-3p level in hPASMCs was obviously upregulated with the increasing dose of PDGF-BB. MiR-382-3p mimic promoted yet miR-382-3p inhibitor suppressed hPASMC proliferation. MiR-382-3p directly targeted ATG7. ATG7 overexpression repressed hPASMC proliferation and migration, whereas siATG7 exerted the opposite effects. ATG7 overexpression partly neutralized the effects of miR-382-3p mimic on proliferation, migration, and autophagy-related proteins (ATG7, p62, and LC3-Ⅱ/LC3-I) in hPASMCs, whereas siATG7 partly offset the impacts of miR-382-3p inhibitor. MiR-382-3p antagomir reversed CTEPH-induced mPAP elevation, miR-382-3p upregulation, thickening of the pulmonary artery wall, and increased expressions of VEGF, PCNA, and autophagy-related proteins in rats, while miR-382-3p agomir potentiated these effects induced by CTEPH.

Conclusion: Overexpressed miR-382-3p promotes vascular remodeling via ATG7 inhibition in CTEPH.

Keywords: ATG7; Autophagy; Chronic thromboembolic pulmonary hypertension; MiR-382-3p; Vascular remodeling.