Evidence map›Paper›PMID 24213632›Full record

ArticleNature2013

Dysfunctional nitric oxide signalling increases risk of myocardial infarction.

Jeanette Erdmann, Klaus Stark, Ulrike B Esslinger, Philipp Moritz Rumpf, Doris Koesling, Cor de Wit, Frank J Kaiser, Diana Braunholz, Anja Medack, Marcus Fischer and 33 more

Registry-linked trialAbstract read
PubMed Publisher
In one paragraph

Article in Nature, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02146872 (Premature Coronary Artery Disease - Clinical and Molecular Genetic Aspects), which is not on this map. Cited by 140 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
140citing papers in PubMed, 6 pooled it
16.0field-weighted citation impact, top 1% 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.

NCT02146872 unknown statusnot on this mapstarted 2014, after this paper: background citation

Premature Coronary Artery Disease - Clinical and Molecular Genetic Aspects

TypeobservationalSponsorAarhus University Hospital SkejbyRan2014 to 2016Enrolled400ConditionsCoronary Artery Disease, Myocardial Infarction, Atherosclerosis
3 · Its place in the literature

Who cites it

140 citing papers in PubMed, 6 syntheses or guidelines pooled it, 277 citations in OpenAlex.

  1. Pooled it
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  4. Pooled it
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  6. Pooled it
  7. Trial
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  9. Review
  10. Review
  11. Chaperonin in health and disease.Molecular biomedicine · 2026
    Review
  12. Article
  13. Article
  14. Soluble guanylyl cyclase, the NO receptor, drives vasorelaxation via endothelial S-nitrosation.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Article
  20. Article

80 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

43 authors at 18 institutions in 9 countries.

Jeanette Erdmann1] Institut für Integrative und Experimentelle Genomik, Universität zu Lübeck, 23562 Lübeck, Germany [2] German Centre for Cardiovascular Research (DZHK), partner site Hamburg/Lübeck/Kiel, 23562 Lübeck, Germany [3].
Klaus Stark1] Klinik und Poliklinik für Innere Medizin II, Universitätsklinikum Regensburg, 93053 Regensburg, Germany [2] Department of Genetic Epidemiology, University of Regensburg, 93053 Regensburg, Germany [3].
Ulrike B Esslinger1] Klinik und Poliklinik für Innere Medizin II, Universitätsklinikum Regensburg, 93053 Regensburg, Germany [2] Institut National de la Santé et de la Recherche Médicale (INSERM), UMR-S937 Paris, France [3].
Philipp Moritz Rumpf1] Deutsches Herzzentrum München and 1. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, 80636 München, Germany [2] German Centre for Cardiovascular Research (DZHK), partner site Munich Heart Alliance, 80636 Munich, Germany [3].
Doris KoeslingDepartment of Pharmacology and Toxicology, Ruhr-University Bochum, 44801 Bochum, Germany.
Cor de Wit1] German Centre for Cardiovascular Research (DZHK), partner site Hamburg/Lübeck/Kiel, 23562 Lübeck, Germany [2] Institut für Physiologie, Universität zu Lübeck, 23562 Lübeck, Germany.
Frank J Kaiser1] German Centre for Cardiovascular Research (DZHK), partner site Hamburg/Lübeck/Kiel, 23562 Lübeck, Germany [2] Institut für Humangenetik, Universität zu Lübeck, 23562 Lübeck, Germany.
Diana BraunholzInstitut für Humangenetik, Universität zu Lübeck, 23562 Lübeck, Germany.
Anja MedackInstitut für Integrative und Experimentelle Genomik, Universität zu Lübeck, 23562 Lübeck, Germany.
Marcus FischerKlinik und Poliklinik für Innere Medizin II, Universitätsklinikum Regensburg, 93053 Regensburg, Germany.
Martina E ZimmermannKlinik und Poliklinik für Innere Medizin II, Universitätsklinikum Regensburg, 93053 Regensburg, Germany.
Stephanie TennstedtInstitut für Integrative und Experimentelle Genomik, Universität zu Lübeck, 23562 Lübeck, Germany.
Elisabeth Graf1] Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany [2] Institute of Human Genetics, Technische Universität München, 81675 München, Germany.
Sebastian Eck1] Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany [2] Institute of Human Genetics, Technische Universität München, 81675 München, Germany.
Zouhair Aherrahrou1] Institut für Integrative und Experimentelle Genomik, Universität zu Lübeck, 23562 Lübeck, Germany [2] German Centre for Cardiovascular Research (DZHK), partner site Hamburg/Lübeck/Kiel, 23562 Lübeck, Germany.
Janja NahrstaedtInstitut für Integrative und Experimentelle Genomik, Universität zu Lübeck, 23562 Lübeck, Germany.
Christina Willenborg1] Institut für Integrative und Experimentelle Genomik, Universität zu Lübeck, 23562 Lübeck, Germany [2] German Centre for Cardiovascular Research (DZHK), partner site Hamburg/Lübeck/Kiel, 23562 Lübeck, Germany.
Petra BruseInstitut für Integrative und Experimentelle Genomik, Universität zu Lübeck, 23562 Lübeck, Germany.
Ingrid BrænneInstitut für Integrative und Experimentelle Genomik, Universität zu Lübeck, 23562 Lübeck, Germany.
Markus M Nöthen1] Institute of Human Genetics, University of Bonn, 53127 Bonn, Germany [2] Department of Genomics, Research Center Life & Brain, University of Bonn, 53127 Bonn, Germany.
Per Hofmann1] Institute of Human Genetics, University of Bonn, 53127 Bonn, Germany [2] Division of Medical Genetics, University Hospital Basel and Department of Biomedicine, University of Basel, 4003 Basel, Switzerland.
Peter S Braund1] Department of Cardiovascular Sciences, University of Leicester, Leicester LE1 7RH, UK [2] Leicester National Institute for Health Research Biomedical Research Unit in Cardiovascular Disease, Glenfield Hospital, Leicester LE1 7RH, UK.
Evanthia MergiaDepartment of Pharmacology and Toxicology, Ruhr-University Bochum, 44801 Bochum, Germany.
Wibke Reinhard1] Deutsches Herzzentrum München and 1. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, 80636 München, Germany [2] German Centre for Cardiovascular Research (DZHK), partner site Munich Heart Alliance, 80636 Munich, Germany.
Christof BurgdorfDeutsches Herzzentrum München and 1. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, 80636 München, Germany.
Stefan SchreiberInstitute of Clinical Molecular Biology, Christian-Albrecht-Universität, 24105 Kiel, Germany.
Anthony J BalmforthDivision of Cardiovascular and Diabetes Research, Multidisciplinary Cardiovascular Research Centre, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds LS2 9JT, UK.
Alistair S HallDivision of Cardiovascular and Neuronal Remodelling, Multidisciplinary Cardiovascular Research Centre, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds LS2 9JT, UK.
Lars BertramDepartment of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany.
Elisabeth Steinhagen-ThiessenCharité Research Group on Geriatrics, Charité-Universitätsmedizin, 10117 Berlin, Germany.
Shu-Chen Li1] Center for Lifespan Psychology, Max Planck Institute for Human Development, 14195 Berlin, Germany [2] Department of Psychology, TU Dresden, 01062 Dresden, Germany.
Winfried März1] Synlab Academy and Business Development, synlab Services GmbH, 68165 Mannheim, Germany [2] Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, 8036 Graz, Austria [3] Medical Clinic V, Medical Faculty Mannheim, University of Heidelberg, 68167 Mannheim, Germany.
Muredach ReillyThe Cardiovascular Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Sekar Kathiresan1] Cardiovascular Research Center and Cardiology Division, Massachusetts General Hospital, Boston, Massachusetts 02215, USA [2] Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts 02215, USA [3] Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts 02215, USA.
Ruth McPhersonUniversity of Ottawa, Heart Institute, Ottawa, Ontario K1Y 4W7, Canada.
Ulrich Walter1] Centrum für Thrombose und Hämostase (CTH), Universitätsmedizin Mainz, 55131 Mainz, Germany [2] German Centre for Cardiovascular Research (DZHK), partner site RheinMain, 55131 Mainz, Germany.
CARDIoGRAM
Jurg Ott1] Institute of Psychology, Chinese Academy of Sciences, Beijing 100864, China [2] Laboratory of Statistical Genetics, Rockefeller University, New York 10065, USA.
Nilesh J Samani1] Department of Cardiovascular Sciences, University of Leicester, Leicester LE1 7RH, UK [2] Leicester National Institute for Health Research Biomedical Research Unit in Cardiovascular Disease, Glenfield Hospital, Leicester LE1 7RH, UK.
Tim M Strom1] Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany [2] Institute of Human Genetics, Technische Universität München, 81675 München, Germany.
Thomas Meitinger1] Deutsches Herzzentrum München and 1. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, 80636 München, Germany [2] Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany [3] Institute of Human Genetics, Technische Universität München, 81675 München, Germany.
Christian Hengstenberg1] Deutsches Herzzentrum München and 1. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, 80636 München, Germany [2] German Centre for Cardiovascular Research (DZHK), partner site Munich Heart Alliance, 80636 Munich, Germany.
Heribert Schunkert1] Deutsches Herzzentrum München and 1. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, 80636 München, Germany [2] German Centre for Cardiovascular Research (DZHK), partner site Munich Heart Alliance, 80636 Munich, Germany.
Institute for Integrative and Experimental Genomics · DETUM Klinikum · DEUniversity Hospital Regensburg · DEGerman Centre for Cardiovascular Research · DEHelmholtz Zentrum München · DEUniversity of Leeds · GBBroad Institute · USGlenfield Hospital · GBUniversity of Bonn · DEUniversity of Leicester · GBInserm · FRJohannes Gutenberg University Mainz · DEMax Planck Institute for Human Development · DEMax Planck Institute for Molecular Genetics · DEMedical University of Graz · ATSynlab Czech (Czechia) · CZUniversity of Lübeck · DEUniversity of Ottawa · CA

Funding

British Heart FoundationDepartment of Health NF-SI-0611-10170
6 · The paper itself

Abstract

Myocardial infarction, a leading cause of death in the Western world, usually occurs when the fibrous cap overlying an atherosclerotic plaque in a coronary artery ruptures. The resulting exposure of blood to the atherosclerotic material then triggers thrombus formation, which occludes the artery. The importance of genetic predisposition to coronary artery disease and myocardial infarction is best documented by the predictive value of a positive family history. Next-generation sequencing in families with several affected individuals has revolutionized mutation identification. Here we report the segregation of two private, heterozygous mutations in two functionally related genes, GUCY1A3 (p.Leu163Phefs*24) and CCT7 (p.Ser525Leu), in an extended myocardial infarction family. GUCY1A3 encodes the α1 subunit of soluble guanylyl cyclase (α1-sGC), and CCT7 encodes CCTη, a member of the tailless complex polypeptide 1 ring complex, which, among other functions, stabilizes soluble guanylyl cyclase. After stimulation with nitric oxide, soluble guanylyl cyclase generates cGMP, which induces vasodilation and inhibits platelet activation. We demonstrate in vitro that mutations in both GUCY1A3 and CCT7 severely reduce α1-sGC as well as β1-sGC protein content, and impair soluble guanylyl cyclase activity. Moreover, platelets from digenic mutation carriers contained less soluble guanylyl cyclase protein and consequently displayed reduced nitric-oxide-induced cGMP formation. Mice deficient in α1-sGC protein displayed accelerated thrombus formation in the microcirculation after local trauma. Starting with a severely affected family, we have identified a link between impaired soluble-guanylyl-cyclase-dependent nitric oxide signalling and myocardial infarction risk, possibly through accelerated thrombus formation. Reversing this defect may provide a new therapeutic target for reducing the risk of myocardial infarction.

Indexed as

Signal TransductionAnimalsChaperonin Containing TCP-1Cyclic GMPDisease SusceptibilityExomeFemaleGenetic Predisposition to DiseaseGuanylate CyclaseHEK293 CellsHumansMaleMiceMutationMyocardial InfarctionNitric OxideCCT7 protein, humanChaperonin Containing TCP-1Cyclic GMPGuanylate CyclaseGUCY1A2 protein, humanGucy1a3 protein, mouseNitric OxideReceptors, Cytoplasmic and NuclearSoluble Guanylyl Cyclase

Identifiers

PMID24213632
OpenAlexW1998507098

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Registered trials

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.