Evidence map›Paper›PMID 40940812›Full record

ArticleCells2025

miR-451 Is a Driver of Lipotoxic Injury in Patients with Diabetic Cardiomyopathy.

Sarah Costantino, Shafeeq A Mohammed, Federico Ranocchi, Francesco Zito, Valentina Delfine, Nazha Hamdani, Maria Cristina Vinci, Giovanni Melina, Francesco Paneni

Abstract read
In one paragraph

Article in Cells, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
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0citing papers in PubMed
–field-weighted citation impact
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

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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

9 authors.

Sarah CostantinoCenter for Translational and Experimental Cardiology (CTEC), Department of Cardiology, University Hospital Zurich and University of Zürich, 8952 Schlieren, Switzerland.
Shafeeq A MohammedCenter for Translational and Experimental Cardiology (CTEC), Department of Cardiology, University Hospital Zurich and University of Zürich, 8952 Schlieren, Switzerland.
Federico RanocchiDepartment of Cardiac Surgery, Sant'Andrea Hospital, "Sapienza" University, Via di Grottarossa, 1035 Rome, Italy.
Francesco ZitoDepartment of Cardiac Surgery, Sant'Andrea Hospital, "Sapienza" University, Via di Grottarossa, 1035 Rome, Italy.ORCID 0009-0002-0213-3651
Valentina DelfineCenter for Translational and Experimental Cardiology (CTEC), Department of Cardiology, University Hospital Zurich and University of Zürich, 8952 Schlieren, Switzerland.
Nazha HamdaniInstitute of Physiology, Ruhr University, 44801 Bochum, Germany.
Maria Cristina VinciCentro Cardiologico Monzino IRCCS, Via C. Parea 4, 20138 Milan, Italy.ORCID 0000-0001-6323-147X
Giovanni MelinaDepartment of Cardiac Surgery, Sant'Andrea Hospital, "Sapienza" University, Via di Grottarossa, 1035 Rome, Italy.
Francesco PaneniCenter for Translational and Experimental Cardiology (CTEC), Department of Cardiology, University Hospital Zurich and University of Zürich, 8952 Schlieren, Switzerland.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

MicroRNA 451 (miR-451) is emerging as a pivotal mediator of cardiac damage in experimental models of diabetic cardiomyopathy. Whether miR-451 plays a detrimental role in the human diabetic myocardium is unknown. The present study investigates miR-451's role in patients with type 2 diabetes (T2D). We show that miR-451 is upregulated in myocardial specimens from T2D patients compared to controls without diabetes and correlates with cardiometabolic parameters, the myocardial triglyceride content and cardiac expression of lipotoxic genes as well as echocardiographic indices of left ventricular dysfunction. Calcium-binding protein 39 (Cab39)-a known target of miR-451 in mouse hearts-was downregulated in T2D patients vs. controls, and its expression negatively correlated with that of miR-451. In cultured human cardiomyocytes (CMs), Ago2 immunoprecipitation confirmed Cab39 to be a direct target of miR-451. Treatment with a high amount of glucose (25mM) and palmitic acid (PA) mimicked miR-451 upregulation and Cab39 downregulation in human CMs. These changes were associated with increased TGs and markers of lipotoxic injury, such as elevated oxidative stress levels, mitochondrial dysfunction and apoptosis. Targeting miR-451 led to restoration of Cab39 levels while rescuing diabetes-induced lipotoxic injury and metabolic dysfunction. By contrast, miR-451 overexpression recapitulated features of lipotoxic damage. Our findings indicate miR-451 to be a potential target for the prevention of myocardial lipotoxic injury in diabetes.

Indexed as

Diabetic CardiomyopathiesMicroRNAsAnimalsApoptosisCalcium-Binding ProteinsDiabetes Mellitus, Type 2FemaleGlucoseHumansMaleMiceMiddle AgedMyocardiumMyocytes, CardiacOxidative StressPalmitic AcidCalcium-Binding ProteinsGlucoseMicroRNAsMIRN451 microRNA, humanPalmitic Acidcardiometabolic diseasediabetesepigeneticsHFpEFlipotoxicitymicroRNA

Identifiers

PMID40940812
PMCPMC12427974

What Socratic 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 Socratic graph.