Evidence mapPaperPMID 33192545Full record

ArticleFrontiers in physiology2020

Tribbles Homolog 3-Mediated Vascular Insulin Resistance Contributes to Hypoxic Pulmonary Hypertension in Intermittent Hypoxia Rat Model.

Fang Fan, Jinxiao He, Hui Su, Haifeng Zhang, Hao Wang, Qianqian Dong, Minghua Zeng, Wenjuan Xing, Xin Sun

Open access · goldAbstract read
In one paragraph

Article in Frontiers in physiology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.5field-weighted citation impact, top 29% 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

4 citing papers in PubMed, 9 citations in OpenAlex.

  1. Article
  2. Article
  3. Frontiers in genetics · 2022
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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 3 institutions in 1 country.

Fang FanDepartment of Pediatrics, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Jinxiao HeDepartment of Pediatrics, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Hui SuDepartment of Geratology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Haifeng ZhangTeaching Experiment Center, Fourth Military Medical University, Xi'an, China.
Hao WangDepartment of Pediatrics, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Qianqian DongDepartment of Natural Medicine, School of Pharmacy, Fourth Military Medical University, Xi'an, China.
Minghua ZengDepartment of Pediatrics, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Wenjuan XingSchool of Aerospace Medicine, Fourth Military Medical University, Xi'an, China.
Xin SunDepartment of Pediatrics, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Air Force Medical University · CNXijing Hospital · CNChina Astronaut Research and Training Center · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

This study aimed to investigate the role of vascular insulin resistance (VIR) and Tribbles homolog 3 (TRIB3) in the pathogenesis of hypoxia-induced pulmonary hypertension (HPH). Rats were subjected to low air pressure and low oxygen intermittently for 4 weeks to induce HPH. The mean right ventricular pressure (mRVP), mean pulmonary arterial pressure (mPAP), and right ventricular index (RVI) were significantly increased in HPH rats. Pulmonary arteries from HPH rats showed VIR with reduced vasodilating effect of insulin. The protein levels of peroxisome proliferator-activated receptor gamma (PPARγ), phosphoinositide 3-kinase (PI3K), phosphorylations of Akt, and endothelial nitric oxide (NO) synthase (eNOS) were decreased, and TRIB3 and phosphorylated extracellular signal-regulated protein kinases (ERK1/2) were increased in pulmonary arteries of HPH rats. Early treatment of pioglitazone (PIO) partially reversed the development of HPH, improved insulin-induced vasodilation, and alleviated the imbalance of the insulin signaling. The overexpression of TRIB3 in rat pulmonary arterial endothelial cells (PAECs) reduced the levels of PPARγ, PI3K, phosphorylated Akt (p-Akt), and phosphorylated eNOS (p-eNOS) and increased p-ERK1/2 and the synthesis of endothelin-1 (ET-1), which were further intensified under hypoxic conditions. Moreover, TRIB3 knockdown caused significant improvement in Akt and eNOS phosphorylations and, otherwise, a reduction of ERK1/2 activation in PAECs after hypoxia. In conclusion, impaired insulin-induced pulmonary vasodilation and the imbalance of insulin-induced signaling mediated by TRIB3 upregulation in the endothelium contribute to the development of HPH. Early PIO treatment improves vascular insulin sensitivity that may help to limit the progression of hypoxic pulmonary hypertension.

Indexed as

hypoxic pulmonary hypertensionproliferator-activated receptor gammapulmonary arterial endotheliumTribbles homolog 3vascular insulin resistance

Identifiers

PMID33192545
PMCPMC7662151
OpenAlexW3096046625

What Socratic holds

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Registered trials

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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 Socratic graph.