Evidence mapPaperPMID 37729634Full record

ArticleHypertension (Dallas, Tex. : 1979)2023

Type 1 Diabetes Impairs Endothelium-Dependent Relaxation Via Increasing Endothelial Cell Glycolysis Through Advanced Glycation End Products, PFKFB3, and Nox1-Mediated Mechanisms.

Reem T Atawia, Robert K Batori, Coleton R Jordan, Simone Kennard, Galina Antonova, Thiago Bruder-Nascimento, Vinay Mehta, Muhammad I Saeed, Vijay S Patel, Tohru Fukai and 4 more

Open access · greenAbstract read
In one paragraph

Article in Hypertension (Dallas, Tex. : 1979), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
3.4field-weighted citation impact, top 7% 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

12 citing papers in PubMed, 18 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Article
  6. Endothelial Metabolic Reprogramming Links Diabetes to Atherosclerosis.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026
    Review
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
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

14 authors at 2 institutions in 1 country.

Reem T AtawiaVascular Biology Center (R.T.A., R.K.B., C.R.J., S.K., G.A., T.B.-N., V.M., T.F., M.U.-F., Y.H., D.J.R.F., E.J.B.d.C.), Medical College of Georgia, Augusta University.
Robert K BatoriVascular Biology Center (R.T.A., R.K.B., C.R.J., S.K., G.A., T.B.-N., V.M., T.F., M.U.-F., Y.H., D.J.R.F., E.J.B.d.C.), Medical College of Georgia, Augusta University.ORCID 0000-0002-1400-6732
Coleton R JordanVascular Biology Center (R.T.A., R.K.B., C.R.J., S.K., G.A., T.B.-N., V.M., T.F., M.U.-F., Y.H., D.J.R.F., E.J.B.d.C.), Medical College of Georgia, Augusta University.
Simone KennardVascular Biology Center (R.T.A., R.K.B., C.R.J., S.K., G.A., T.B.-N., V.M., T.F., M.U.-F., Y.H., D.J.R.F., E.J.B.d.C.), Medical College of Georgia, Augusta University.
Galina AntonovaVascular Biology Center (R.T.A., R.K.B., C.R.J., S.K., G.A., T.B.-N., V.M., T.F., M.U.-F., Y.H., D.J.R.F., E.J.B.d.C.), Medical College of Georgia, Augusta University.
Thiago Bruder-NascimentoVascular Biology Center (R.T.A., R.K.B., C.R.J., S.K., G.A., T.B.-N., V.M., T.F., M.U.-F., Y.H., D.J.R.F., E.J.B.d.C.), Medical College of Georgia, Augusta University.ORCID 0000-0001-5671-318X
Vinay MehtaVascular Biology Center (R.T.A., R.K.B., C.R.J., S.K., G.A., T.B.-N., V.M., T.F., M.U.-F., Y.H., D.J.R.F., E.J.B.d.C.), Medical College of Georgia, Augusta University.
Muhammad I SaeedDepartment of Surgery (M.I.S., V.S.P.), Medical College of Georgia, Augusta University.
Vijay S PatelDepartment of Surgery (M.I.S., V.S.P.), Medical College of Georgia, Augusta University.ORCID 0000-0002-8402-2682
Tohru FukaiVascular Biology Center (R.T.A., R.K.B., C.R.J., S.K., G.A., T.B.-N., V.M., T.F., M.U.-F., Y.H., D.J.R.F., E.J.B.d.C.), Medical College of Georgia, Augusta University.ORCID 0000-0001-9864-571X
Masuko Ushio-FukaiVascular Biology Center (R.T.A., R.K.B., C.R.J., S.K., G.A., T.B.-N., V.M., T.F., M.U.-F., Y.H., D.J.R.F., E.J.B.d.C.), Medical College of Georgia, Augusta University.ORCID 0000-0001-7048-2381
Yuqing HuoVascular Biology Center (R.T.A., R.K.B., C.R.J., S.K., G.A., T.B.-N., V.M., T.F., M.U.-F., Y.H., D.J.R.F., E.J.B.d.C.), Medical College of Georgia, Augusta University.ORCID 0000-0002-0305-4122
David J R FultonVascular Biology Center (R.T.A., R.K.B., C.R.J., S.K., G.A., T.B.-N., V.M., T.F., M.U.-F., Y.H., D.J.R.F., E.J.B.d.C.), Medical College of Georgia, Augusta University.ORCID 0000-0002-1528-1517
Eric J Belin de ChantemèleVascular Biology Center (R.T.A., R.K.B., C.R.J., S.K., G.A., T.B.-N., V.M., T.F., M.U.-F., Y.H., D.J.R.F., E.J.B.d.C.), Medical College of Georgia, Augusta University.ORCID 0000-0002-0184-3830
Augusta University · USTwitter (United States) · US

Funding

Mechanism of cardiovascular disease in premenopausal womenR01HL155265 · NHLBI · AUGUSTA UNIVERSITY · PI Eric J Belin de Chantemele · 2022 to 2024
$1.6M
Redox Regulation of Cu Importer CTR1 in AngiogenesisR01HL147550 · NHLBI · AUGUSTA UNIVERSITY · PI TOHRU FUKAI, Masuko Ushio-Fukai · 2022 to 2023
$1.5M
Vascular Extracellular Superoxide Dismutase ModulationR01HL070187 · EMORY UNIVERSITY · 2002 to 2005
$1.1M
Leptin in HIV associated vascular diseasesR01HL147639 · NHLBI · AUGUSTA UNIVERSITY · PI Eric J Belin de Chantemele · 2022 to 2023
$997k
American Heart Association-American Stroke Association 971863NHLBI NIH HHS R01 HL070187NHLBI NIH HHS R01 HL116976NHLBI NIH HHS R01 HL133613NHLBI NIH HHS R01 HL147550NHLBI NIH HHS R01 HL147639NHLBI NIH HHS R01 HL155265NHLBI NIH HHS R01 HL156646NHLBI NIH HHS R01 HL160014
6 · The paper itself

Abstract

backgroundType 1 diabetes (T1D) is a major cause of endothelial dysfunction. Although cellular bioenergetics has been identified as a new regulator of vascular function, whether glycolysis, the primary bioenergetic pathway in endothelial cells (EC), regulates vascular tone and contributes to impaired endothelium-dependent relaxation (EDR) in T1D remains unknown.

methodsExperiments were conducted in Akita mice with intact or selective deficiency in EC PFKFB3 (6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3), the main regulator of glycolysis. Seahorse analyzer and myography were employed to measure glycolysis and mitochondrial respiration, and EDR, respectively, in aortic explants. EC PFKFB3 (Ad-PFKFB3) and glycolysis (Ad-GlycoHi) were increased in situ via adenoviral transduction.

resultsT1D increased EC glycolysis and elevated EC expression of PFKFB3 and NADPH oxidase Nox1 (NADPH oxidase homolog 1). Functionally, pharmacological and genetic inhibition of PFKFB3 restored EDR in T1D, while in situ aorta EC transduction with Ad-PFKFB3 or Ad-GlycoHi reproduced the impaired EDR associated with T1D. Nox1 inhibition restored EDR in aortic rings from Akita mice, as well as in Ad-PFKFB3-transduced aorta EC and lactate-treated wild-type aortas. T1D increased the expression of the advanced glycation end product precursor methylglyoxal in the aortas. Exposure of the aortas to methylglyoxal impaired EDR, which was prevented by PFKFB3 inhibition. T1D and exposure to methylglyoxal increased EC expression of HIF1α (hypoxia-inducible factor 1α), whose inhibition blunted methylglyoxal-mediated EC PFKFB3 upregulation.

conclusionsEC bioenergetics, namely glycolysis, is a new regulator of vasomotion and excess glycolysis, a novel mechanism of endothelial dysfunction in T1D. We introduce excess methylglyoxal, HIF1α, and PFKFB3 as major effectors in T1D-mediated increased EC glycolysis.

Indexed as

Diabetes Mellitus, Type 1Endothelial CellsAnimalsEndotheliumGlycolysisMicePyruvaldehydePyruvaldehydeaortadiabetes mellitus, type 1endothelial cellsglycolysismetabolismvascular diseasesvasodilatation

Identifiers

PMID37729634
PMCPMC10514399
OpenAlexW4385986146

What Socratic holds

Textmetadata
LicenceTDM
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 Socratic graph.