ArticleMolecular medicine (Cambridge, Mass.)2022
Farnesyl diphosphate synthase regulated endothelial proliferation and autophagy during rat pulmonary arterial hypertension induced by monocrotaline.
Article in Molecular medicine (Cambridge, Mass.), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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10 citing papers in PubMed, 17 citations in OpenAlex.
- GLSP ameliorates monocrotaline-induced pulmonary arterial hypertension through inhibition of the PI3K/AKT and MAPK signaling pathways.Journal of molecular histology · 2026Article
- Exploring Lipid Metabolic Reprogramming: Mechanistic Insights and Implications for Tumor Radiotherapy.International journal of biological sciences · 2026Review
- Neutrophil-derived extracellular vesicles in the plasma of alpha-1 antitrypsin deficient individuals reveal pro-inflammatory metabolic and transcriptomic signatures.Extracellular vesicle · 2025Article
- Identification and validation of SQLE in steroid-induced osteonecrosis of the femoral head: a bioinformatics and experimental study.Journal of orthopaedic surgery and research · 2025Article
- Maternal Electronic Cigarette Exposure Induces Dysregulation of Autophagy via Oxidative Stress/DNA Methylation in Pulmonary Hypertension Offspring.Current medical science · 2025Article
- Targeting endothelial cells: the pathological mechanisms and therapeutic innovations in pulmonary arterial hypertension.Frontiers in cell and developmental biology · 2025Review
- Exosomes enriched by miR-429-3p derived from ITGB1 modified Telocytes alleviates hypoxia-induced pulmonary arterial hypertension through regulating Rac1 expression.Cell biology and toxicology · 2024Article
- Modulation of the RAC1/MAPK/ERK signalling pathway by farnesyl diphosphate synthase regulates granulosa cells proliferation in polycystic ovary syndrome.Human cell · 2024Article
- Molecular regulation and therapeutic implications of cell death in pulmonary hypertension.Cell death discovery · 2023Review
- Epigenetic regulation of programmed cell death in hypoxia-induced pulmonary arterial hypertension.Frontiers in immunology · 2023Review
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9 authors at 1 institution in 1 country.
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Abstract
backgroundThe proliferation ability and autophagy level of pulmonary artery endothelial cells (PAECs) play an important role in promoting the development of pulmonary artery hypertension (PAH), and there is still no effective treatment for PAH. Farnesyl diphosphate synthase (FDPS) is a key enzyme in the mevalonate pathway. The intermediate metabolites of this pathway are closely related to the activity of autophagy-associated small G proteins, including Ras-related C3 botulinum toxin substrate 1 (Rac1). Studies have shown that the mevalonate pathway affects the activation levels of different small G proteins, autophagy signaling pathways, vascular endothelial function, and so on. However, the exact relationship between them is still unclear in PAH.
methodIn vitro, western blotting and mRFP-GFP-LC3 puncta formation assays were used to observe the expression of FDPS and the level of autophagy in PAECs treated with monocrotaline pyrrole (MCTP). In addition, cell proliferation and migration assays were used to assess the effect of FDPS on endothelial function, and Rac1 activity assays were used to evaluate the effect of Rac1 activation on PAEC autophagy via the PI3K/AKT/mTOR signaling pathway. In vivo, the right heart catheterization method, hematoxylin and eosin (H&E) staining and western blotting were used to determine the effect of FDPS on PAEC autophagy and monocrotaline (MCT)-induced PAH.
resultsWe show that the expression of FDPS is increased in the PAH module in vitro and in vivo, concomitant with the induction of autophagy and the activation of Rac1. Our data demonstrate that inhibition of FDPS ameliorates endothelial function and decreases MCT-induced autophagy levels. Mechanistically, we found that FDPS promotes autophagy, Rac1 activity and endothelial disfunction through the PI3K/AKT/mTOR signaling pathway.
conclusionOur study suggests that FDPS contributes to active small G protein-induced autophagy during MCT-induced PAH, which may serve as a potential therapeutic target against PAH.
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