Evidence map›Paper›PMID 33494625›Full record

ArticleCirculation research2021

BH4 Increases nNOS Activity and Preserves Left Ventricular Function in Diabetes.

Ricardo Carnicer, Drew Duglan, Klemen Ziberna, Alice Recalde, Svetlana Reilly, Jillian N Simon, Simona Mafrici, Ritu Arya, Esther Roselló-Lletí, Surawee Chuaiphichai and 4 more

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In one paragraph

Article in Circulation research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
2.8field-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

14 citing papers in PubMed, 24 citations in OpenAlex.

  1. Article
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  8. Targeting ferroptosis: a novel insight against myocardial infarction and ischemia-reperfusion injuries.Apoptosis : an international journal on programmed cell death · 2023
    Review
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  11. Tetrahydrobiopterin (BHBiomedicines · 2022
    Article
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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

14 authors at 2 institutions in 3 countries.

Ricardo CarnicerCardiovascular Medicine (R.C., D.D., K.Z., A.R., S.R., J.N.S., S.M., R.A., E.R., S.C., C.A.L., K.M.C., B.C.), University of Oxford, Oxford United Kingdom.
Drew DuglanCardiovascular Medicine (R.C., D.D., K.Z., A.R., S.R., J.N.S., S.M., R.A., E.R., S.C., C.A.L., K.M.C., B.C.), University of Oxford, Oxford United Kingdom.
Klemen ZibernaCardiovascular Medicine (R.C., D.D., K.Z., A.R., S.R., J.N.S., S.M., R.A., E.R., S.C., C.A.L., K.M.C., B.C.), University of Oxford, Oxford United Kingdom.
Alice RecaldeCardiovascular Medicine (R.C., D.D., K.Z., A.R., S.R., J.N.S., S.M., R.A., E.R., S.C., C.A.L., K.M.C., B.C.), University of Oxford, Oxford United Kingdom.
Svetlana ReillyCardiovascular Medicine (R.C., D.D., K.Z., A.R., S.R., J.N.S., S.M., R.A., E.R., S.C., C.A.L., K.M.C., B.C.), University of Oxford, Oxford United Kingdom.
Jillian N SimonCardiovascular Medicine (R.C., D.D., K.Z., A.R., S.R., J.N.S., S.M., R.A., E.R., S.C., C.A.L., K.M.C., B.C.), University of Oxford, Oxford United Kingdom.
Simona MafriciCardiovascular Medicine (R.C., D.D., K.Z., A.R., S.R., J.N.S., S.M., R.A., E.R., S.C., C.A.L., K.M.C., B.C.), University of Oxford, Oxford United Kingdom.
Ritu AryaCardiovascular Medicine (R.C., D.D., K.Z., A.R., S.R., J.N.S., S.M., R.A., E.R., S.C., C.A.L., K.M.C., B.C.), University of Oxford, Oxford United Kingdom.
Esther Roselló-LletíCardiovascular Medicine (R.C., D.D., K.Z., A.R., S.R., J.N.S., S.M., R.A., E.R., S.C., C.A.L., K.M.C., B.C.), University of Oxford, Oxford United Kingdom.
Surawee ChuaiphichaiCardiovascular Medicine (R.C., D.D., K.Z., A.R., S.R., J.N.S., S.M., R.A., E.R., S.C., C.A.L., K.M.C., B.C.), University of Oxford, Oxford United Kingdom.
Damian TylerPhysiology, Anatomy and Genetics (D.T.), University of Oxford, Oxford United Kingdom.
Craig A LygateCardiovascular Medicine (R.C., D.D., K.Z., A.R., S.R., J.N.S., S.M., R.A., E.R., S.C., C.A.L., K.M.C., B.C.), University of Oxford, Oxford United Kingdom.
Keith M ChannonCardiovascular Medicine (R.C., D.D., K.Z., A.R., S.R., J.N.S., S.M., R.A., E.R., S.C., C.A.L., K.M.C., B.C.), University of Oxford, Oxford United Kingdom.
Barbara CasadeiCardiovascular Medicine (R.C., D.D., K.Z., A.R., S.R., J.N.S., S.M., R.A., E.R., S.C., C.A.L., K.M.C., B.C.), University of Oxford, Oxford United Kingdom.
Anna Needs Neuroblastoma Answers · USUniversity of Oxford · GB

Funding

British Heart Foundation CH/12/3/29609British Heart Foundation CH/16/1/32013British Heart Foundation FS/14/17/30634British Heart Foundation FS/15/15/31364British Heart Foundation FS/19/18/34252British Heart Foundation RE/13/1/30181British Heart Foundation RG/07/003/23133British Heart Foundation RG/11/15/29375British Heart Foundation RG/12/5/29576British Heart Foundation RG/16/12/32451British Heart Foundation RG/17/10/32859British Heart Foundation RG/18/12/34040
6 · The paper itself

Abstract

rationaleIn diabetic patients, heart failure with predominant left ventricular (LV) diastolic dysfunction is a common complication for which there is no effective treatment. Oxidation of the NOS (nitric oxide synthase) cofactor tetrahydrobiopterin (BH4) and dysfunctional NOS activity have been implicated in the pathogenesis of the diabetic vascular and cardiomyopathic phenotype.

objectiveUsing mice models and human myocardial samples, we evaluated whether and by which mechanism increasing myocardial BH4 availability prevented or reversed LV dysfunction induced by diabetes. METHODS AND

resultsIn contrast to the vascular endothelium, BH4 levels, superoxide production, and NOS activity (by liquid chromatography) did not differ in the LV myocardium of diabetic mice or in atrial tissue from diabetic patients. Nevertheless, the impairment in both cardiomyocyte relaxation and [Ca

conclusionsWe uncovered a novel mechanism whereby myocardial BH4 prevents and reverses LV diastolic and systolic dysfunction associated with diabetes via an nNOS-mediated increase in insulin-independent myocardial glucose uptake and utilization. These findings highlight the potential of GCH1/BH4-based therapeutics in human diabetic cardiomyopathy. Graphic Abstract: A graphic abstract is available for this article.

Indexed as

AnimalsBiopterinsDiabetic CardiomyopathiesGlucoseGlucose Transporter Type 1GlutathioneGTP CyclohydrolaseHEK293 CellsHumansMiceMice, Inbred C57BLMyocytes, CardiacNitric Oxide Synthase Type IVentricular Dysfunction, LeftBiopterinsGch1 protein, mouseGlucoseGlucose Transporter Type 1GlutathioneGTP CyclohydrolaseNitric Oxide Synthase Type IsapropterinSlc2a1 protein, mousecardiovascular diseaseglucoseheart failuremicenitric oxide synthase

Identifiers

PMID33494625
PMCPMC7612785
OpenAlexW3123753277

What OpenQuestion holds

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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.