Evidence map›Paper›PMID 29386187›Full record

ArticleCirculation research2018

Enhanced Redox State and Efficiency of Glucose Oxidation With miR Based Suppression of Maladaptive NADPH-Dependent Malic Enzyme 1 Expression in Hypertrophied Hearts.

Ryan Lahey, Andrew N Carley, Xuerong Wang, Carley E Glass, Kevin D Accola, Scott Silvestry, J Michael O'Donnell, E Douglas Lewandowski

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
3.1field-weighted citation impact, top 8% 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

31 citing papers in PubMed, 43 citations in OpenAlex.

  1. Review
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  3. Sestrin2 serves as a scaffold protein to maintain cardiac energy and metabolic homeostasis during pathological stress.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024
    Review
  4. Review
  5. UCP1-dependent brown adipose activation accelerates cardiac metabolic remodeling and reduces initial hypertrophic and fibrotic responses to pathological stress.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024
    Article
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  7. Advances in Metabolic Remodeling and Intervention Strategies in Heart Failure.Journal of cardiovascular translational research · 2024
    Review
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  10. Metabolic flux in the driver's seat during cardiac health and disease.Journal of molecular and cellular cardiology · 2023
    Review
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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

8 authors at 4 institutions in 1 country.

Ryan LaheyFrom the Department of Internal Medicine and Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus (A.N.C., E.D.L.); Sanford Burnham Prebys Medical Discovery Institute, Orlando, FL (A.N.C., C.E.G., E.D.L.); Center for Cardiovascular Research, University of Illinois College of Medicine at Chicago (R.L., A.N.C., X.W., J.M.O., E.D.L.); and Translational Research Institute for Diabetes and Metabolism (C.E.G., E.D.L.) and Department of Surgery, Florida Hospital Cardiovascular Institute, Florida Hospital Transplant Center (K.D.A., S.S.), Florida Hospital, Orlando.
Andrew N CarleyFrom the Department of Internal Medicine and Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus (A.N.C., E.D.L.); Sanford Burnham Prebys Medical Discovery Institute, Orlando, FL (A.N.C., C.E.G., E.D.L.); Center for Cardiovascular Research, University of Illinois College of Medicine at Chicago (R.L., A.N.C., X.W., J.M.O., E.D.L.); and Translational Research Institute for Diabetes and Metabolism (C.E.G., E.D.L.) and Department of Surgery, Florida Hospital Cardiovascular Institute, Florida Hospital Transplant Center (K.D.A., S.S.), Florida Hospital, Orlando.
Xuerong WangFrom the Department of Internal Medicine and Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus (A.N.C., E.D.L.); Sanford Burnham Prebys Medical Discovery Institute, Orlando, FL (A.N.C., C.E.G., E.D.L.); Center for Cardiovascular Research, University of Illinois College of Medicine at Chicago (R.L., A.N.C., X.W., J.M.O., E.D.L.); and Translational Research Institute for Diabetes and Metabolism (C.E.G., E.D.L.) and Department of Surgery, Florida Hospital Cardiovascular Institute, Florida Hospital Transplant Center (K.D.A., S.S.), Florida Hospital, Orlando.
Carley E GlassFrom the Department of Internal Medicine and Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus (A.N.C., E.D.L.); Sanford Burnham Prebys Medical Discovery Institute, Orlando, FL (A.N.C., C.E.G., E.D.L.); Center for Cardiovascular Research, University of Illinois College of Medicine at Chicago (R.L., A.N.C., X.W., J.M.O., E.D.L.); and Translational Research Institute for Diabetes and Metabolism (C.E.G., E.D.L.) and Department of Surgery, Florida Hospital Cardiovascular Institute, Florida Hospital Transplant Center (K.D.A., S.S.), Florida Hospital, Orlando.
Kevin D AccolaFrom the Department of Internal Medicine and Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus (A.N.C., E.D.L.); Sanford Burnham Prebys Medical Discovery Institute, Orlando, FL (A.N.C., C.E.G., E.D.L.); Center for Cardiovascular Research, University of Illinois College of Medicine at Chicago (R.L., A.N.C., X.W., J.M.O., E.D.L.); and Translational Research Institute for Diabetes and Metabolism (C.E.G., E.D.L.) and Department of Surgery, Florida Hospital Cardiovascular Institute, Florida Hospital Transplant Center (K.D.A., S.S.), Florida Hospital, Orlando.
Scott SilvestryFrom the Department of Internal Medicine and Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus (A.N.C., E.D.L.); Sanford Burnham Prebys Medical Discovery Institute, Orlando, FL (A.N.C., C.E.G., E.D.L.); Center for Cardiovascular Research, University of Illinois College of Medicine at Chicago (R.L., A.N.C., X.W., J.M.O., E.D.L.); and Translational Research Institute for Diabetes and Metabolism (C.E.G., E.D.L.) and Department of Surgery, Florida Hospital Cardiovascular Institute, Florida Hospital Transplant Center (K.D.A., S.S.), Florida Hospital, Orlando.
J Michael O'DonnellFrom the Department of Internal Medicine and Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus (A.N.C., E.D.L.); Sanford Burnham Prebys Medical Discovery Institute, Orlando, FL (A.N.C., C.E.G., E.D.L.); Center for Cardiovascular Research, University of Illinois College of Medicine at Chicago (R.L., A.N.C., X.W., J.M.O., E.D.L.); and Translational Research Institute for Diabetes and Metabolism (C.E.G., E.D.L.) and Department of Surgery, Florida Hospital Cardiovascular Institute, Florida Hospital Transplant Center (K.D.A., S.S.), Florida Hospital, Orlando.
E Douglas LewandowskiFrom the Department of Internal Medicine and Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus (A.N.C., E.D.L.); Sanford Burnham Prebys Medical Discovery Institute, Orlando, FL (A.N.C., C.E.G., E.D.L.); Center for Cardiovascular Research, University of Illinois College of Medicine at Chicago (R.L., A.N.C., X.W., J.M.O., E.D.L.); and Translational Research Institute for Diabetes and Metabolism (C.E.G., E.D.L.) and Department of Surgery, Florida Hospital Cardiovascular Institute, Florida Hospital Transplant Center (K.D.A., S.S.), Florida Hospital, Orlando. doug.lewandowski@osumc.edu.
University of Illinois Chicago · USUniversity of Illinois Urbana-Champaign · USDiscovery Institute · USIllinois College · US

Funding

Magnetic Resonance of Cardiac C13 Flux &Metabolic RateR37HL049244 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI LEWANDOWSKI, E DOUGLAS · 2003 to 2012
$5.8M
Magnetic Resonance of Cardiac C13 Flux & Metabolism RateR01HL049244 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI LEWANDOWSKI, E DOUGLAS · 1993 to 2018
$3.7M
Maladaptive Expression of Metabolic Enzymes and Activity in Heart FailureR01HL132525 · NHLBI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI LEWANDOWSKI, E DOUGLAS · 2016 to 2019
$2.5M
NHLBI NIH HHS R01 HL049244NHLBI NIH HHS R01 HL132525NHLBI NIH HHS R37 HL049244
6 · The paper itself

Abstract

rationaleMetabolic remodeling in hypertrophic hearts includes inefficient glucose oxidation via increased anaplerosis fueled by pyruvate carboxylation. Pyruvate carboxylation to malate through elevated ME1 (malic enzyme 1) consumes NADPH necessary for reduction of glutathione and maintenance of intracellular redox state.

objectiveTo elucidate upregulated ME1 as a potential maladaptive mechanism for inefficient glucose oxidation and compromised redox state in hypertrophied hearts. METHODS AND

resultsME1 expression was selectively inhibited, in vivo, via non-native miR-ME1 (miRNA specific to ME1) in pressure-overloaded rat hearts. Rats subjected to transverse aortic constriction (TAC) or Sham surgery received either miR-ME1 or PBS. Effects of ME1 suppression on anaplerosis and reduced glutathione (GSH) content were studied in isolated hearts supplied

conclusionsA maladaptive increase in anaplerosis via ME1 in TAC is associated with reduced GSH content. Suppressing increased ME1 expression in hypertrophied rat hearts, which is also elevated in failing human hearts, reduced pyruvate carboxylation thereby normalizing anaplerosis, restoring GSH content, and reducing lactate accumulation. Reducing ME1 induced favorable metabolic shifts for carbohydrate oxidation, improving intracellular redox state and enhanced cardiac performance in pathological hypertrophy.

Indexed as

AgedAnimalsCardiomegalyGlucoseGlutathioneHumansMalate DehydrogenaseMaleMicroRNAsMiddle AgedMyocardiumNADPOxidation-ReductionPyruvic AcidRatsRats, Sprague-DawleyGlucoseGlutathioneMalate Dehydrogenasemalate dehydrogenase (decarboxylating)MicroRNAsNADPPyruvic Acidglucoseheart failurehypertrophymetabolismmicroRNAs

Identifiers

PMID29386187
PMCPMC6463492
OpenAlexW2791740039

What OpenQuestion holds

Textmetadata
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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 OpenQuestion graph.