Acute pulmonary embolism (APE) is a common cause of acute cardiovascular failure and has a high morbidity and mortality rate. Inhibiting the excessive proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) is a potential treatment strategy following an APE. Various microRNAs (miRNAs/miRs) have been shown to regulate cell proliferation, apoptosis and other physiological processes. However, the specific mechanisms underlying the action of multiple miRNAs are still not understood in APE. In the present study, the role of miR‑106b‑5p on APE was demonstrated in platelet‑derived growth factor (PDGF)‑induced PASMCs in vitro and in an APE‑mouse model in vivo. The results showed that miR‑106b‑5p expression was downregulated in PDGF‑induced PASMCs and APE mice, and NOR1 levels were upregulated. Proliferating cell nuclear antigen (PCNA) expression levels in cells and proliferation of PASMCs proliferation and migration were reduced following treatment with miR‑106b‑5p agomiR, and increased following treatment with miR‑106b‑5p antagomiR. miR‑106b‑5p targeted the 3' untranslated region of NOR‑1 mRNA and reduced NOR1 expression. NOR1 overexpression reversed the effects of miR‑106‑5p on PDGF‑induced PASMCs. The functional roles of miR‑106b‑5p in PDGF‑induced PASMCs and an APE mouse‑model, and the underlying molecular mechanisms were evaluated. AgomiR‑106b‑5p improved APE‑induced mortality and pulmonary vascular proliferation in mice. These data suggest that miR‑106‑5p is a novel regulator of proliferation of PASMCs and of pulmonary vascular remodeling through PDGF‑induced PASMCs in an APE mouse model via targeting NOR1. These results expand the understanding of the pathogenesis underlying APE and highlight potential novel therapeutic targets.
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http://dx.doi.org/10.3892/ijmm.2020.4532 | DOI Listing |
Eur J Med Chem
January 2025
Department of Medicinal Chemistry, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410013, Hunan, China; Hunan Key Laboratory of Diagnostic and Therapeutic Drug Research for Chronic Diseases, Changsha, 410013, Hunan, China; Hunan Key Laboratory of Organ Fibrosis, Changsha, 410013, Hunan, China. Electronic address:
AMP-activated protein kinase (AMPK), a heterotrimeric serine-threonine kinase, has been identified as a promising target for regulating vascular remodeling in pulmonary arterial hypertension (PAH) due to its capacity to promote proliferation, autophagy, and anti-apoptosis in pulmonary artery smooth muscle cells (PASMCs). However, research into AMPK inhibitors is very limited. Herein, a virtual screening strategy was employed to identify CHEMBL3780091 as a lead compound for a series of novel AMPK inhibitors by exploring the structure-activity relationship around a specific pyridine-2-one scaffold.
View Article and Find Full Text PDFRedox Biol
January 2025
Department of Pediatrics, Peking University First Hospital, Beijing, 100034, PR China. Electronic address:
Background: The binding of endothelin-1 (ET-1) to endothelin type A receptor (ETAR) performs a critical action in pulmonary arterial smooth muscle cell (PASMC) proliferation leading to pulmonary vascular structural remodeling. More evidence showed that cystathionine γ-lyase (CSE)-catalyzed endogenous hydrogen sulfide (HS) was involved in the pathogenesis of cardiovascular diseases. In this study, we aimed to explore the effect of endogenous HS/CSE pathway on the ET-1/ETAR binding and its underlying mechanisms in the cellular and animal models of PASMC proliferation.
View Article and Find Full Text PDFJ Surg Res
January 2025
Department of Neonatology, Children's Hospital Affiliated to Shandong University, Jinan, ShanDong, China. Electronic address:
Introduction: Sildenafil, a selective phosphodiesterase 5 inhibitor, modulates vascular dysfunction, with hypoxia-induced pulmonary artery smooth muscle cells (PASMCs) proliferation, migration, and invasion closely implicated in vascular remodeling in persistent pulmonary hypertension of the newborn (PPHN). This study aimed to assess sildenafil's protective effects against PPHN and elucidate underlying molecular pathways.
Methods: Cell Counting Kit-8, wound healing, and Transwell assays evaluated rat PASMC proliferation, migration, and invasion under hypoxia.
Int J Biol Macromol
January 2025
Central Laboratory of Harbin Medical University (Daqing), Daqing 163319, PR China; College of Pharmacy, Harbin Medical University, Harbin 150081, PR China; Key Laboratory of Cardiovascular Medicine Research, Ministry of Education, Harbin Medical University, Harbin 150081, PR China. Electronic address:
Pulmonary hypertension (PH) is a malignant cardiovascular disease with a complex etiology. 5-Methylcytosine (m5C) is a post-transcriptional RNA modification identified in both stable and highly abundant RNAs, with a lower frequency of occurrence in circular RNAs (circRNAs). Nevertheless, the function of m5C-modified circRNAs in the pathogenesis of PH remains uncertain.
View Article and Find Full Text PDFInt J Biol Macromol
January 2025
College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang, 330045, PR China. Electronic address:
Due to the lack of specific antibody anti-chicken tumor necrosis factor receptor-associated factor 2 (TRAF2), it is difficult to further explore the role of TRAF2 in pulmonary artery remodeling in pulmonary hypertension(PH) in broilers. In this experiment, we prepared a polyclonal antibody to TRAF2 by constructing a TRAF2 recombinant protein prokaryotic expression vector and analyzed the expression of TRAF2 in in vivo and in vitro models of pulmonary hypertension in broiler chickens and the effect of TRAF2 on the activity and apoptosis of PASMCs. The results showed that after immunization with TRAF2 recombinant protein we obtained high titers of polyclonal antibodies, and astragalus polysaccharide as an immune adjuvant could enhance the effect of immunization.
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