Evidence map›Paper›PMID 36376492›Full record

ArticleHypertension research : official journal of the Japanese Society of Hypertension2023

Augmented O-GlcNAcylation exacerbates right ventricular dysfunction and remodeling via enhancement of hypertrophy, mitophagy, and fibrosis in mice exposed to long-term intermittent hypoxia.

Shunichi Yokoe, Tetsuya Hayashi, Takatoshi Nakagawa, Ryuji Kato, Yoshio Ijiri, Takehiro Yamaguchi, Yasukatsu Izumi, Minoru Yoshiyama, Michio Asahi

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Article in Hypertension research : official journal of the Japanese Society of Hypertension, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.6field-weighted citation impact, top 17% 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

6 citing papers in PubMed, 18 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

Shunichi YokoeDepartment of Pharmacology, Faculty of Medicine, Osaka Medical and Pharmaceutical University, Osaka, Japan.
Tetsuya HayashiDepartment of Pharmacology, Faculty of Medicine, Osaka Medical and Pharmaceutical University, Osaka, Japan.
Takatoshi NakagawaDepartment of Pharmacology, Faculty of Medicine, Osaka Medical and Pharmaceutical University, Osaka, Japan.
Ryuji KatoDepartment of Cardiovascular Pharmacotherapy and Toxicology, Faculty of Pharmacy, Osaka Medical and Pharmaceutical University, Osaka, Japan.
Yoshio IjiriDepartment of Cardiovascular Pharmacotherapy and Toxicology, Faculty of Pharmacy, Osaka Medical and Pharmaceutical University, Osaka, Japan.
Takehiro YamaguchiDepartment of Cardiovascular Medicine, Faculty of Medicine, Osaka Metropolitan University, Osaka, Japan.
Yasukatsu IzumiDepartment of Pharmacology, Faculty of Medicine, Osaka Metropolitan University, Osaka, Japan.
Minoru YoshiyamaDepartment of Cardiovascular Medicine, Faculty of Medicine, Osaka Metropolitan University, Osaka, Japan.
Michio AsahiDepartment of Pharmacology, Faculty of Medicine, Osaka Medical and Pharmaceutical University, Osaka, Japan. masahi@ompu.ac.jp.
Osaka University of Pharmaceutical Sciences · JPTokyo Metropolitan University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Previously, we showed that augmented O-linked N-acetylglucosaminylation (O-GlcNAcylation) mitigates cardiac remodeling in O-GlcNAc transferase-transgenic (Ogt-Tg) mice exposed to acute (2-week) intermittent hypoxia (IH) by suppressing nuclear factor of activated T cells (NFAT) and nuclear factor kappa B (NF-κB) via the O-GlcNAcylation of glycogen synthase kinase 3 beta (GSK-3β) and NF-κB p65. Because this effect is time dependent, we exposed Ogt-Tg mice to IH for 4 weeks (IH4W) in the present study. O-GlcNAcylation was significantly enhanced in Ogt-Tg mice vs. wild-type (WT) mice exposed to normoxia and IH4W. Total O-GlcNAcylation levels were significantly increased in WT and Ogt-Tg mice after IH4W vs. normoxia. After IH4W, Ogt-Tg mice displayed significantly exacerbated signs of cardiac hypertrophy and fibrosis in the right ventricles (RVs) but not the left ventricles (LVs). Echocardiography revealed IH4W-induced right ventricular dysfunction. Phosphorylated GSK-3β levels were increased in Ogt-Tg mice vs. WT mice after IH4W, whereas phosphorylated NF-κB p65 levels were unaffected. Mitophagy, which is associated with cardiac dysfunction, was increased in the RVs of Ogt-Tg mice after IH4W. Furthermore, the levels of phosphorylated dynamin-related protein 1 (p-Drp1) were significantly increased, and the expression of mitofusin-2 (MFN2) was significantly decreased. In human embryonic kidney cells, mitochondrial uncoupler-induced mitochondrial dysfunction was accelerated in Ogt-overexpressing cells. In addition to increasing the levels of phosphorylated Smad2, IH4W promoted cardiac fibrosis in the RVs of Ogt-Tg mice. Thus, augmented O-GlcNAcylation may aggravate IH4W-induced right ventricular dysfunction and remodeling by promoting hypertrophy, mitophagy, and fibrosis via GSK-3β inactivation, an increased p-Drp-1/MFN2 ratio, and Smad2 activation, respectively.

Indexed as

NF-kappa BVentricular Dysfunction, RightAnimalsCardiomegalyFibrosisGlycogen Synthase Kinase 3 betaHumansHypoxiaMiceMice, TransgenicMitophagyGlycogen Synthase Kinase 3 betaNF-kappa BCardiac remodelingIntermittent hypoxiaO-GlcNAcylation

Identifiers

PMID36376492
OpenAlexW4309042858

What OpenQuestion holds

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Read underepoch 390

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 OpenQuestion graph.