Evidence map›Paper›PMID 29255073›Full record

ArticleHypertension (Dallas, Tex. : 1979)2018

MicroRNA-221/222 Family Counteracts Myocardial Fibrosis in Pressure Overload-Induced Heart Failure.

Robin Verjans, Tim Peters, Francisco Javier Beaumont, Rick van Leeuwen, Tessa van Herwaarden, Wouter Verhesen, Chantal Munts, Mitchell Bijnen, Michiel Henkens, Javier Diez and 7 more

Open access · bronzeAbstract read
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Article in Hypertension (Dallas, Tex. : 1979), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 114 papers.

0numbers the graph read from it
0cells of the map it votes in
114citing papers in PubMed
5.2field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

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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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3 · Its place in the literature

Who cites it

114 citing papers in PubMed, 170 citations in OpenAlex.

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  20. Heart failure with preserved ejection fraction in pigs causes shifts in posttranscriptional checkpoints.American journal of physiology. Heart and circulatory physiology · 2024
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54 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors at 5 institutions in 2 countries.

Robin VerjansFrom the Department of Cardiology (R.V., T.P., R.v.L., W.V., M.H., L.J.d.W., S.H., B.S.), Department of Physiology (C.M., F.A.v.N., M.v.B.), and Department of Internal Medicine (M.B.), CARIM School for Cardiovascular Diseases, Maastricht University, The Netherlands; Program of Cardiovascular Diseases, Centre for Applied Medical Research, University of Navarra, Pamplona, Spain (F.J.B., J.D., A.G.); Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain (F.J.B., J.D., A.G.); CIBERCV, Carlos III Institute of Health, Madrid, Spain (F.J.B., J.D., A.G.); Department of Molecular Cell Biology, Leiden University Medical Biology Center, The Netherlands (T.v.H., M.J.G.); Department of Cardiology and Cardiac Surgery, University of Navarra Clinic, Pamplona, Spain (J.D.); Netherlands Heart Institute (ICIN), Utrecht; and Department of Cardiovascular Sciences, Centre for Molecular and Vascular Biology (CMVB), KU Leuven, Belgium (S.H.).
Tim PetersFrom the Department of Cardiology (R.V., T.P., R.v.L., W.V., M.H., L.J.d.W., S.H., B.S.), Department of Physiology (C.M., F.A.v.N., M.v.B.), and Department of Internal Medicine (M.B.), CARIM School for Cardiovascular Diseases, Maastricht University, The Netherlands; Program of Cardiovascular Diseases, Centre for Applied Medical Research, University of Navarra, Pamplona, Spain (F.J.B., J.D., A.G.); Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain (F.J.B., J.D., A.G.); CIBERCV, Carlos III Institute of Health, Madrid, Spain (F.J.B., J.D., A.G.); Department of Molecular Cell Biology, Leiden University Medical Biology Center, The Netherlands (T.v.H., M.J.G.); Department of Cardiology and Cardiac Surgery, University of Navarra Clinic, Pamplona, Spain (J.D.); Netherlands Heart Institute (ICIN), Utrecht; and Department of Cardiovascular Sciences, Centre for Molecular and Vascular Biology (CMVB), KU Leuven, Belgium (S.H.).
Francisco Javier BeaumontFrom the Department of Cardiology (R.V., T.P., R.v.L., W.V., M.H., L.J.d.W., S.H., B.S.), Department of Physiology (C.M., F.A.v.N., M.v.B.), and Department of Internal Medicine (M.B.), CARIM School for Cardiovascular Diseases, Maastricht University, The Netherlands; Program of Cardiovascular Diseases, Centre for Applied Medical Research, University of Navarra, Pamplona, Spain (F.J.B., J.D., A.G.); Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain (F.J.B., J.D., A.G.); CIBERCV, Carlos III Institute of Health, Madrid, Spain (F.J.B., J.D., A.G.); Department of Molecular Cell Biology, Leiden University Medical Biology Center, The Netherlands (T.v.H., M.J.G.); Department of Cardiology and Cardiac Surgery, University of Navarra Clinic, Pamplona, Spain (J.D.); Netherlands Heart Institute (ICIN), Utrecht; and Department of Cardiovascular Sciences, Centre for Molecular and Vascular Biology (CMVB), KU Leuven, Belgium (S.H.).
Rick van LeeuwenFrom the Department of Cardiology (R.V., T.P., R.v.L., W.V., M.H., L.J.d.W., S.H., B.S.), Department of Physiology (C.M., F.A.v.N., M.v.B.), and Department of Internal Medicine (M.B.), CARIM School for Cardiovascular Diseases, Maastricht University, The Netherlands; Program of Cardiovascular Diseases, Centre for Applied Medical Research, University of Navarra, Pamplona, Spain (F.J.B., J.D., A.G.); Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain (F.J.B., J.D., A.G.); CIBERCV, Carlos III Institute of Health, Madrid, Spain (F.J.B., J.D., A.G.); Department of Molecular Cell Biology, Leiden University Medical Biology Center, The Netherlands (T.v.H., M.J.G.); Department of Cardiology and Cardiac Surgery, University of Navarra Clinic, Pamplona, Spain (J.D.); Netherlands Heart Institute (ICIN), Utrecht; and Department of Cardiovascular Sciences, Centre for Molecular and Vascular Biology (CMVB), KU Leuven, Belgium (S.H.).
Tessa van HerwaardenFrom the Department of Cardiology (R.V., T.P., R.v.L., W.V., M.H., L.J.d.W., S.H., B.S.), Department of Physiology (C.M., F.A.v.N., M.v.B.), and Department of Internal Medicine (M.B.), CARIM School for Cardiovascular Diseases, Maastricht University, The Netherlands; Program of Cardiovascular Diseases, Centre for Applied Medical Research, University of Navarra, Pamplona, Spain (F.J.B., J.D., A.G.); Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain (F.J.B., J.D., A.G.); CIBERCV, Carlos III Institute of Health, Madrid, Spain (F.J.B., J.D., A.G.); Department of Molecular Cell Biology, Leiden University Medical Biology Center, The Netherlands (T.v.H., M.J.G.); Department of Cardiology and Cardiac Surgery, University of Navarra Clinic, Pamplona, Spain (J.D.); Netherlands Heart Institute (ICIN), Utrecht; and Department of Cardiovascular Sciences, Centre for Molecular and Vascular Biology (CMVB), KU Leuven, Belgium (S.H.).
Wouter VerhesenFrom the Department of Cardiology (R.V., T.P., R.v.L., W.V., M.H., L.J.d.W., S.H., B.S.), Department of Physiology (C.M., F.A.v.N., M.v.B.), and Department of Internal Medicine (M.B.), CARIM School for Cardiovascular Diseases, Maastricht University, The Netherlands; Program of Cardiovascular Diseases, Centre for Applied Medical Research, University of Navarra, Pamplona, Spain (F.J.B., J.D., A.G.); Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain (F.J.B., J.D., A.G.); CIBERCV, Carlos III Institute of Health, Madrid, Spain (F.J.B., J.D., A.G.); Department of Molecular Cell Biology, Leiden University Medical Biology Center, The Netherlands (T.v.H., M.J.G.); Department of Cardiology and Cardiac Surgery, University of Navarra Clinic, Pamplona, Spain (J.D.); Netherlands Heart Institute (ICIN), Utrecht; and Department of Cardiovascular Sciences, Centre for Molecular and Vascular Biology (CMVB), KU Leuven, Belgium (S.H.).
Chantal MuntsFrom the Department of Cardiology (R.V., T.P., R.v.L., W.V., M.H., L.J.d.W., S.H., B.S.), Department of Physiology (C.M., F.A.v.N., M.v.B.), and Department of Internal Medicine (M.B.), CARIM School for Cardiovascular Diseases, Maastricht University, The Netherlands; Program of Cardiovascular Diseases, Centre for Applied Medical Research, University of Navarra, Pamplona, Spain (F.J.B., J.D., A.G.); Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain (F.J.B., J.D., A.G.); CIBERCV, Carlos III Institute of Health, Madrid, Spain (F.J.B., J.D., A.G.); Department of Molecular Cell Biology, Leiden University Medical Biology Center, The Netherlands (T.v.H., M.J.G.); Department of Cardiology and Cardiac Surgery, University of Navarra Clinic, Pamplona, Spain (J.D.); Netherlands Heart Institute (ICIN), Utrecht; and Department of Cardiovascular Sciences, Centre for Molecular and Vascular Biology (CMVB), KU Leuven, Belgium (S.H.).
Mitchell BijnenFrom the Department of Cardiology (R.V., T.P., R.v.L., W.V., M.H., L.J.d.W., S.H., B.S.), Department of Physiology (C.M., F.A.v.N., M.v.B.), and Department of Internal Medicine (M.B.), CARIM School for Cardiovascular Diseases, Maastricht University, The Netherlands; Program of Cardiovascular Diseases, Centre for Applied Medical Research, University of Navarra, Pamplona, Spain (F.J.B., J.D., A.G.); Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain (F.J.B., J.D., A.G.); CIBERCV, Carlos III Institute of Health, Madrid, Spain (F.J.B., J.D., A.G.); Department of Molecular Cell Biology, Leiden University Medical Biology Center, The Netherlands (T.v.H., M.J.G.); Department of Cardiology and Cardiac Surgery, University of Navarra Clinic, Pamplona, Spain (J.D.); Netherlands Heart Institute (ICIN), Utrecht; and Department of Cardiovascular Sciences, Centre for Molecular and Vascular Biology (CMVB), KU Leuven, Belgium (S.H.).
Michiel HenkensFrom the Department of Cardiology (R.V., T.P., R.v.L., W.V., M.H., L.J.d.W., S.H., B.S.), Department of Physiology (C.M., F.A.v.N., M.v.B.), and Department of Internal Medicine (M.B.), CARIM School for Cardiovascular Diseases, Maastricht University, The Netherlands; Program of Cardiovascular Diseases, Centre for Applied Medical Research, University of Navarra, Pamplona, Spain (F.J.B., J.D., A.G.); Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain (F.J.B., J.D., A.G.); CIBERCV, Carlos III Institute of Health, Madrid, Spain (F.J.B., J.D., A.G.); Department of Molecular Cell Biology, Leiden University Medical Biology Center, The Netherlands (T.v.H., M.J.G.); Department of Cardiology and Cardiac Surgery, University of Navarra Clinic, Pamplona, Spain (J.D.); Netherlands Heart Institute (ICIN), Utrecht; and Department of Cardiovascular Sciences, Centre for Molecular and Vascular Biology (CMVB), KU Leuven, Belgium (S.H.).
Javier DiezFrom the Department of Cardiology (R.V., T.P., R.v.L., W.V., M.H., L.J.d.W., S.H., B.S.), Department of Physiology (C.M., F.A.v.N., M.v.B.), and Department of Internal Medicine (M.B.), CARIM School for Cardiovascular Diseases, Maastricht University, The Netherlands; Program of Cardiovascular Diseases, Centre for Applied Medical Research, University of Navarra, Pamplona, Spain (F.J.B., J.D., A.G.); Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain (F.J.B., J.D., A.G.); CIBERCV, Carlos III Institute of Health, Madrid, Spain (F.J.B., J.D., A.G.); Department of Molecular Cell Biology, Leiden University Medical Biology Center, The Netherlands (T.v.H., M.J.G.); Department of Cardiology and Cardiac Surgery, University of Navarra Clinic, Pamplona, Spain (J.D.); Netherlands Heart Institute (ICIN), Utrecht; and Department of Cardiovascular Sciences, Centre for Molecular and Vascular Biology (CMVB), KU Leuven, Belgium (S.H.).
Leon J de WindtFrom the Department of Cardiology (R.V., T.P., R.v.L., W.V., M.H., L.J.d.W., S.H., B.S.), Department of Physiology (C.M., F.A.v.N., M.v.B.), and Department of Internal Medicine (M.B.), CARIM School for Cardiovascular Diseases, Maastricht University, The Netherlands; Program of Cardiovascular Diseases, Centre for Applied Medical Research, University of Navarra, Pamplona, Spain (F.J.B., J.D., A.G.); Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain (F.J.B., J.D., A.G.); CIBERCV, Carlos III Institute of Health, Madrid, Spain (F.J.B., J.D., A.G.); Department of Molecular Cell Biology, Leiden University Medical Biology Center, The Netherlands (T.v.H., M.J.G.); Department of Cardiology and Cardiac Surgery, University of Navarra Clinic, Pamplona, Spain (J.D.); Netherlands Heart Institute (ICIN), Utrecht; and Department of Cardiovascular Sciences, Centre for Molecular and Vascular Biology (CMVB), KU Leuven, Belgium (S.H.).
Frans A van NieuwenhovenFrom the Department of Cardiology (R.V., T.P., R.v.L., W.V., M.H., L.J.d.W., S.H., B.S.), Department of Physiology (C.M., F.A.v.N., M.v.B.), and Department of Internal Medicine (M.B.), CARIM School for Cardiovascular Diseases, Maastricht University, The Netherlands; Program of Cardiovascular Diseases, Centre for Applied Medical Research, University of Navarra, Pamplona, Spain (F.J.B., J.D., A.G.); Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain (F.J.B., J.D., A.G.); CIBERCV, Carlos III Institute of Health, Madrid, Spain (F.J.B., J.D., A.G.); Department of Molecular Cell Biology, Leiden University Medical Biology Center, The Netherlands (T.v.H., M.J.G.); Department of Cardiology and Cardiac Surgery, University of Navarra Clinic, Pamplona, Spain (J.D.); Netherlands Heart Institute (ICIN), Utrecht; and Department of Cardiovascular Sciences, Centre for Molecular and Vascular Biology (CMVB), KU Leuven, Belgium (S.H.).
Marc van BilsenFrom the Department of Cardiology (R.V., T.P., R.v.L., W.V., M.H., L.J.d.W., S.H., B.S.), Department of Physiology (C.M., F.A.v.N., M.v.B.), and Department of Internal Medicine (M.B.), CARIM School for Cardiovascular Diseases, Maastricht University, The Netherlands; Program of Cardiovascular Diseases, Centre for Applied Medical Research, University of Navarra, Pamplona, Spain (F.J.B., J.D., A.G.); Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain (F.J.B., J.D., A.G.); CIBERCV, Carlos III Institute of Health, Madrid, Spain (F.J.B., J.D., A.G.); Department of Molecular Cell Biology, Leiden University Medical Biology Center, The Netherlands (T.v.H., M.J.G.); Department of Cardiology and Cardiac Surgery, University of Navarra Clinic, Pamplona, Spain (J.D.); Netherlands Heart Institute (ICIN), Utrecht; and Department of Cardiovascular Sciences, Centre for Molecular and Vascular Biology (CMVB), KU Leuven, Belgium (S.H.).
Marie José GoumansFrom the Department of Cardiology (R.V., T.P., R.v.L., W.V., M.H., L.J.d.W., S.H., B.S.), Department of Physiology (C.M., F.A.v.N., M.v.B.), and Department of Internal Medicine (M.B.), CARIM School for Cardiovascular Diseases, Maastricht University, The Netherlands; Program of Cardiovascular Diseases, Centre for Applied Medical Research, University of Navarra, Pamplona, Spain (F.J.B., J.D., A.G.); Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain (F.J.B., J.D., A.G.); CIBERCV, Carlos III Institute of Health, Madrid, Spain (F.J.B., J.D., A.G.); Department of Molecular Cell Biology, Leiden University Medical Biology Center, The Netherlands (T.v.H., M.J.G.); Department of Cardiology and Cardiac Surgery, University of Navarra Clinic, Pamplona, Spain (J.D.); Netherlands Heart Institute (ICIN), Utrecht; and Department of Cardiovascular Sciences, Centre for Molecular and Vascular Biology (CMVB), KU Leuven, Belgium (S.H.).
Stephane HeymansFrom the Department of Cardiology (R.V., T.P., R.v.L., W.V., M.H., L.J.d.W., S.H., B.S.), Department of Physiology (C.M., F.A.v.N., M.v.B.), and Department of Internal Medicine (M.B.), CARIM School for Cardiovascular Diseases, Maastricht University, The Netherlands; Program of Cardiovascular Diseases, Centre for Applied Medical Research, University of Navarra, Pamplona, Spain (F.J.B., J.D., A.G.); Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain (F.J.B., J.D., A.G.); CIBERCV, Carlos III Institute of Health, Madrid, Spain (F.J.B., J.D., A.G.); Department of Molecular Cell Biology, Leiden University Medical Biology Center, The Netherlands (T.v.H., M.J.G.); Department of Cardiology and Cardiac Surgery, University of Navarra Clinic, Pamplona, Spain (J.D.); Netherlands Heart Institute (ICIN), Utrecht; and Department of Cardiovascular Sciences, Centre for Molecular and Vascular Biology (CMVB), KU Leuven, Belgium (S.H.).
Arantxa GonzálezFrom the Department of Cardiology (R.V., T.P., R.v.L., W.V., M.H., L.J.d.W., S.H., B.S.), Department of Physiology (C.M., F.A.v.N., M.v.B.), and Department of Internal Medicine (M.B.), CARIM School for Cardiovascular Diseases, Maastricht University, The Netherlands; Program of Cardiovascular Diseases, Centre for Applied Medical Research, University of Navarra, Pamplona, Spain (F.J.B., J.D., A.G.); Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain (F.J.B., J.D., A.G.); CIBERCV, Carlos III Institute of Health, Madrid, Spain (F.J.B., J.D., A.G.); Department of Molecular Cell Biology, Leiden University Medical Biology Center, The Netherlands (T.v.H., M.J.G.); Department of Cardiology and Cardiac Surgery, University of Navarra Clinic, Pamplona, Spain (J.D.); Netherlands Heart Institute (ICIN), Utrecht; and Department of Cardiovascular Sciences, Centre for Molecular and Vascular Biology (CMVB), KU Leuven, Belgium (S.H.).
Blanche SchroenFrom the Department of Cardiology (R.V., T.P., R.v.L., W.V., M.H., L.J.d.W., S.H., B.S.), Department of Physiology (C.M., F.A.v.N., M.v.B.), and Department of Internal Medicine (M.B.), CARIM School for Cardiovascular Diseases, Maastricht University, The Netherlands; Program of Cardiovascular Diseases, Centre for Applied Medical Research, University of Navarra, Pamplona, Spain (F.J.B., J.D., A.G.); Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain (F.J.B., J.D., A.G.); CIBERCV, Carlos III Institute of Health, Madrid, Spain (F.J.B., J.D., A.G.); Department of Molecular Cell Biology, Leiden University Medical Biology Center, The Netherlands (T.v.H., M.J.G.); Department of Cardiology and Cardiac Surgery, University of Navarra Clinic, Pamplona, Spain (J.D.); Netherlands Heart Institute (ICIN), Utrecht; and Department of Cardiovascular Sciences, Centre for Molecular and Vascular Biology (CMVB), KU Leuven, Belgium (S.H.). b.schroen@maastrichtuniversity.nl.
Netherlands Heart Institute · NLCentro de Investigación en Red en Enfermedades Cardiovasculares · ESInstituto de Salud Carlos III · ESLeiden University Medical Center · NLUniversidad de Navarra · ES

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Pressure overload causes cardiac fibroblast activation and transdifferentiation, leading to increased interstitial fibrosis formation and subsequently myocardial stiffness, diastolic and systolic dysfunction, and eventually heart failure. A better understanding of the molecular mechanisms underlying pressure overload-induced cardiac remodeling and fibrosis will have implications for heart failure treatment strategies. The microRNA (miRNA)-221/222 family, consisting of miR-221-3p and miR-222-3p, is differentially regulated in mouse and human cardiac pathology and inversely associated with kidney and liver fibrosis. We investigated the role of this miRNA family during pressure overload-induced cardiac remodeling. In myocardial biopsies of patients with severe fibrosis and dilated cardiomyopathy or aortic stenosis, we found significantly lower miRNA-221/222 levels as compared to matched patients with nonsevere fibrosis. In addition, miRNA-221/222 levels in aortic stenosis patients correlated negatively with the extent of myocardial fibrosis and with left ventricular stiffness. Inhibition of both miRNAs during AngII (angiotensin II)-mediated pressure overload in mice led to increased fibrosis and aggravated left ventricular dilation and dysfunction. In rat cardiac fibroblasts, inhibition of miRNA-221/222 derepressed TGF-β (transforming growth factor-β)-mediated profibrotic SMAD2 (mothers against decapentaplegic homolog 2) signaling and downstream gene expression, whereas overexpression of both miRNAs blunted TGF-β-induced profibrotic signaling. We found that the miRNA-221/222 family may target several genes involved in TGF-β signaling, including JNK1 (c-Jun N-terminal kinase 1), TGF-β receptor 1 and TGF-β receptor 2, and ETS-1 (ETS proto-oncogene 1). Our findings show that heart failure-associated downregulation of the miRNA-221/222 family enables profibrotic signaling in the pressure-overloaded heart.

Indexed as

AnimalsAortic Valve StenosisCardiomyopathiesFibroblastsFibrosisHeart FailureHumansMaleMiceMice, Inbred C57BLMicroRNAsMyocardiumProto-Oncogene MasRatsSignal TransductionTransforming Growth Factor betaMAS1 protein, humanMicroRNAsMIR221, humanMIR222, humanProto-Oncogene MasTransforming Growth Factor betacardiomyopathiesfibroblastsheart failuremicroRNAs

Identifiers

PMID29255073
OpenAlexW2779089668

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