Evidence map›Paper›PMID 35962329›Full record

ArticleMolecular medicine (Cambridge, Mass.)2022

Farnesyl diphosphate synthase regulated endothelial proliferation and autophagy during rat pulmonary arterial hypertension induced by monocrotaline.

Tingting Jin, Jiangting Lu, Qingbo Lv, Yingchao Gong, Zhaojin Feng, Hangying Ying, Meihui Wang, Guosheng Fu, Dongmei Jiang

Open access · goldAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
2.4field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 17 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 1 institution in 1 country.

Tingting Jin *Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 East Qingchun Road, Hangzhou, 310016, Zhejiang, People's Republic of China.
Jiangting Lu *Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 East Qingchun Road, Hangzhou, 310016, Zhejiang, People's Republic of China.
Qingbo LvDepartment of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 East Qingchun Road, Hangzhou, 310016, Zhejiang, People's Republic of China.
Yingchao GongDepartment of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 East Qingchun Road, Hangzhou, 310016, Zhejiang, People's Republic of China.
Zhaojin FengDepartment of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 East Qingchun Road, Hangzhou, 310016, Zhejiang, People's Republic of China.
Hangying YingDepartment of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 East Qingchun Road, Hangzhou, 310016, Zhejiang, People's Republic of China.
Meihui WangKey Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Hangzhou, China.
Guosheng FuDepartment of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 East Qingchun Road, Hangzhou, 310016, Zhejiang, People's Republic of China. fugs@zju.edu.cn.
Dongmei JiangDepartment of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 East Qingchun Road, Hangzhou, 310016, Zhejiang, People's Republic of China. 3312024@zju.edu.cn.ORCID 0000-0001-9597-6986
Sir Run Run Shaw Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

Hypertension, PulmonaryMonomeric GTP-Binding ProteinsPulmonary Arterial HypertensionAnimalsAutophagyCell ProliferationEndothelial CellsGeranyltranstransferaseMevalonic AcidMonocrotalinePhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktPulmonary ArteryRatsRats, Sprague-DawleyTOR Serine-Threonine KinasesGeranyltranstransferaseMevalonic AcidMonocrotalineMonomeric GTP-Binding ProteinsPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktTOR Serine-Threonine KinasesAutophagyEndothelialFarnesyl diphosphate synthaseProliferationPulmonary artery hypertensionRas-related C3 botulinum toxin substrate 1

Identifiers

PMID35962329
PMCPMC9373289
OpenAlexW4291145511

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.