Evidence map›Paper›PMID 28330474›Full record

ArticleLipids in health and disease2017

Hypercholesterolemia downregulates autophagy in the rat heart.

Zoltán Giricz, Gábor Koncsos, Tomáš Rajtík, Zoltán V Varga, Tamás Baranyai, Csaba Csonka, Adrián Szobi, Adriana Adameová, Roberta A Gottlieb, Péter Ferdinandy

Erratum issuedOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Lipids in health and disease, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
2.9field-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

22 citing papers in PubMed, 34 citations in OpenAlex.

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  10. Regulation of the Keap1-Nrf2 Signaling Axis by Glycyrrhetinic Acid Promoted Oxidative Stress-Induced HEvidence-based complementary and alternative medicine : eCAM · 2022
    Article
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  16. Article
  17. Guidelines for evaluating myocardial cell death.American journal of physiology. Heart and circulatory physiology · 2019
    Review
  18. Article
  19. Review
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 4 institutions in 3 countries.

Zoltán GiriczDepartment of Pharmacology and Pharmacotherapy, Faculty of Medicine, Semmelweis University, Nagyvárad tér 4, H-1089, Budapest, Hungary. giricz.zoltan@med.semmelweis-univ.hu.ORCID http://orcid.org/0000-0003-2036-8665
Gábor KoncsosDepartment of Pharmacology and Pharmacotherapy, Faculty of Medicine, Semmelweis University, Nagyvárad tér 4, H-1089, Budapest, Hungary.
Tomáš RajtíkDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University, Odbojárov 10, 83232, Bratislava, Slovakia.
Zoltán V VargaDepartment of Pharmacology and Pharmacotherapy, Faculty of Medicine, Semmelweis University, Nagyvárad tér 4, H-1089, Budapest, Hungary.
Tamás BaranyaiDepartment of Pharmacology and Pharmacotherapy, Faculty of Medicine, Semmelweis University, Nagyvárad tér 4, H-1089, Budapest, Hungary.
Csaba CsonkaDepartment of Biochemistry, Faculty of Medicine, University of Szeged, Dóm tér 9, H-6720, Szeged, Hungary.
Adrián SzobiDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University, Odbojárov 10, 83232, Bratislava, Slovakia.
Adriana AdameováDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University, Odbojárov 10, 83232, Bratislava, Slovakia.
Roberta A GottliebHeart Institute, Cedars-Sinai Medical Center, 127 S. San Vicente Blvd., Los Angeles, CA, 90048, USA.
Péter FerdinandyDepartment of Pharmacology and Pharmacotherapy, Faculty of Medicine, Semmelweis University, Nagyvárad tér 4, H-1089, Budapest, Hungary.
Semmelweis University · HUComenius University Bratislava · SKCedars-Sinai Medical Center · USUniversity of Szeged · HU

Funding

Protein Chemistry and ProteomicsP01HL112730 · NHLBI · SAN DIEGO STATE UNIVERSITY · PI VAN EYK, JENNIFER E · 2013 to 2017
$12.0M
NHLBI NIH HHS P01 HL112730
6 · The paper itself

Abstract

backgroundWe have previously shown that efficiency of ischemic conditioning is diminished in hypercholesterolemia and that autophagy is necessary for cardioprotection. However, it is unknown whether isolated hypercholesterolemia disturbs autophagy or the mammalian target of rapamycin (mTOR) pathways. Therefore, we investigated whether isolated hypercholesterolemia modulates cardiac autophagy-related pathways or programmed cell death mechanisms such as apoptosis and necroptosis in rat heart.

methodsMale Wistar rats were fed either normal chow (NORM; n = 9) or with 2% cholesterol and 0.25% cholic acid-enriched diet (CHOL; n = 9) for 12 weeks. CHOL rats exhibited a 41% increase in plasma total cholesterol level over that of NORM rats (4.09 mmol/L vs. 2.89 mmol/L) at the end of diet period. Animals were sacrificed, hearts were excised and briefly washed out. Left ventricles were snap-frozen for determination of markers of autophagy, mTOR pathway, apoptosis, and necroptosis by Western blot.

resultsIsolated hypercholesterolemia was associated with a significant reduction in expression of cardiac autophagy markers such as LC3-II, Beclin-1, Rubicon and RAB7 as compared to controls. Phosphorylation of ribosomal S6, a surrogate marker for mTOR activity, was increased in CHOL samples. Cleaved caspase-3, a marker of apoptosis, increased in CHOL hearts, while no difference in the expression of necroptotic marker RIP1, RIP3 and MLKL was detected between treatments.

conclusionsThis is the first comprehensive analysis of autophagy and programmed cell death pathways of apoptosis and necroptosis in hearts of hypercholesterolemic rats. Our data show that isolated hypercholesterolemia suppresses basal cardiac autophagy and that the decrease in autophagy may be a result of an activated mTOR pathway. Reduced autophagy was accompanied by increased apoptosis, while cardiac necroptosis was not modulated by isolated hypercholesterolemia. Decreased basal autophagy and elevated apoptosis may be responsible for the loss of cardioprotection reported in hypercholesterolemic animals.

Indexed as

AnimalsApoptosisAutophagyBeclin-1BiomarkersCaspase 3CholesterolCholic AcidDiet, High-FatGene Expression RegulationHeartHypercholesterolemiaMaleMicrotubule-Associated ProteinsNecrosisProtein KinasesAnxa3 protein, ratBeclin-1Becn1 protein, ratBiomarkersCasp3 protein, ratCaspase 3CholesterolCholic AcidMicrotubule-Associated ProteinsMLKL protein, ratmTOR protein, ratProtein KinasesProtein Serine-Threonine Kinasesrab7 GTP-Binding Proteinsrab7 GTP-binding proteins, ratrab GTP-Binding ProteinsReceptor-Interacting Protein Serine-Threonine KinasesRibosomal Protein S6 KinasesRIPK1 protein, ratRipk3 protein, ratTOR Serine-Threonine KinasesApoptosisATG8AutophagyCaspaseHypercholesterolemiaNecroptosisProgrammed necrosisReceptor-interacting serine/threonine-protein kinase

Identifiers

PMID28330474
PMCPMC5363032
OpenAlexW2603642316

What OpenQuestion holds

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LicenceCC BY
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.