Evidence mapPaperPMID 27435231Full record

ArticleJournal of translational medicine2016

Aerobic exercise training protects against endothelial dysfunction by increasing nitric oxide and hydrogen peroxide production in LDL receptor-deficient mice.

Daniele M Guizoni, Gabriel G Dorighello, Helena C F Oliveira, Maria A Delbin, Marta H Krieger, Ana P Davel

Open access · goldAbstract read
In one paragraph

Article in Journal of translational medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 1 pooled it
3.1field-weighted citation impact, top 9% 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

19 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.

  1. Preclinical techniques to investigate exercise training in vascular pathophysiology.American journal of physiology. Heart and circulatory physiology · 2021
    Pooled it
  2. Guidelines for evaluating endothelial function in vascular tissue.American journal of physiology. Heart and circulatory physiology · 2026
    Review
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  5. Time to run: Late rather than early exercise training in mice remodels the gut microbiome and reduces atherosclerosis development.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023
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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

6 authors at 1 institution in 1 country.

Daniele M GuizoniDepartment of Structural and Functional Biology, Institute of Biology, University of Campinas-UNICAMP, P.O. Box 6109, Campinas, São Paulo, Brazil.
Gabriel G DorighelloDepartment of Structural and Functional Biology, Institute of Biology, University of Campinas-UNICAMP, P.O. Box 6109, Campinas, São Paulo, Brazil.
Helena C F OliveiraDepartment of Structural and Functional Biology, Institute of Biology, University of Campinas-UNICAMP, P.O. Box 6109, Campinas, São Paulo, Brazil.
Maria A DelbinDepartment of Structural and Functional Biology, Institute of Biology, University of Campinas-UNICAMP, P.O. Box 6109, Campinas, São Paulo, Brazil.
Marta H KriegerDepartment of Structural and Functional Biology, Institute of Biology, University of Campinas-UNICAMP, P.O. Box 6109, Campinas, São Paulo, Brazil.
Ana P DavelDepartment of Structural and Functional Biology, Institute of Biology, University of Campinas-UNICAMP, P.O. Box 6109, Campinas, São Paulo, Brazil. anapdavel@gmail.com.
Universidade Estadual de Campinas (UNICAMP) · BR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundEndothelial dysfunction associated with hypercholesterolemia is an early event in atherosclerosis characterized by redox imbalance associated with high superoxide production and reduced nitric oxide (NO) and hydrogen peroxide (H2O2) production. Aerobic exercise training (AET) has been demonstrated to ameliorate atherosclerotic lesions and oxidative stress in advanced atherosclerosis. However, whether AET protects against the early mechanisms of endothelial dysfunction in familial hypercholesterolemia remains unclear. This study investigated the effects of AET on endothelial dysfunction and vascular redox status in the aortas of LDL receptor knockout mice (LDLr(-/-)), a genetic model of familial hypercholesterolemia.

methodsTwelve-week-old C57BL/6J (WT) and LDLr(-/-) mice were divided into sedentary and exercised (AET on a treadmill 1 h/5 × per week) groups for 4 weeks. Changes in lipid profiles, endothelial function, and aortic NO, H2O2 and superoxide production were examined.

resultsTotal cholesterol and triglycerides were increased in sedentary and exercised LDLr(-/-) mice. Endothelium-dependent relaxation induced by acetylcholine was impaired in aortas of sedentary LDLr(-/-) mice but not in the exercised group. Inhibition of NO synthase (NOS) activity or H2O2 decomposition by catalase abolished the differences in the acetylcholine response between the animals. No changes were noted in the relaxation response induced by NO donor sodium nitroprusside or H2O2. Neuronal NOS expression and endothelial NOS phosphorylation (Ser1177), as well as NO and H2O2 production, were reduced in aortas of sedentary LDLr(-/-) mice and restored by AET. Incubation with apocynin increased acetylcholine-induced relaxation in sedentary, but not exercised LDLr(-/-) mice, suggesting a minor participation of NADPH oxidase in the endothelium-dependent relaxation after AET. Consistent with these findings, Nox2 expression and superoxide production were reduced in the aortas of exercised compared to sedentary LDLr(-/-) mice. Furthermore, the aortas of sedentary LDLr(-/-) mice showed reduced expression of superoxide dismutase (SOD) isoforms and minor participation of Cu/Zn-dependent SODs in acetylcholine-induced, endothelium-dependent relaxation, abnormalities that were partially attenuated in exercised LDLr(-/-) mice.

conclusionThe data gathered by this study suggest AET as a potential non-pharmacological therapy in the prevention of very early endothelial dysfunction and redox imbalance in familial hypercholesterolemia via increases in NO bioavailability and H2O2 production.

Indexed as

Physical Conditioning, AnimalAcetylcholineAnimalsAorta, ThoracicBody WeightEndothelium, VascularHydrogen PeroxideMice, Inbred C57BLMice, KnockoutNitric OxideNitroprussideReceptors, LDLSerumSuperoxidesAcetylcholineHydrogen PeroxideNitric OxideNitroprussideReceptors, LDLSuperoxidesAerobic exercise trainingEndothelial dysfunctionFamilial hypercholesterolemiaHydrogen peroxideLDL receptor-deficient miceNitric oxide synthaseSuperoxide dismutase

Identifiers

PMID27435231
PMCPMC4950099
OpenAlexW2505569242

What Socratic holds

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LicenceCC BY
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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.