Sildenafil Reduces Neointimal Hyperplasia after Angioplasty and Inhibits Platelet Aggregation via Activation of cGMP-dependent Protein Kinase View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-05-23

AUTHORS

Han-Mo Yang, Sooryeonhwa Jin, Hyunduk Jang, Ju-Young Kim, Joo-Eun Lee, Joonoh Kim, Hyo-Soo Kim

ABSTRACT

Sildenafil is known to reduce cardiac hypertrophy through cGMP-dependent protein kinase (cGK) activation. Studies have demonstrated that cGK has a central switching role in modulating vascular smooth muscle cell (VSMC) phenotype in response to vascular injury. Here, we aimed to examine the effects of cGK activation by sildenafil on neointimal formation and platelet aggregation. After vascular injury, neointimal hyperplasia in rat carotid arteries was significantly reduced in the sildenafil-treated group. This effect of sildenafil was accompanied by the reduction of viability and migration of VSMCs. Further experiments showed that the increased cGK activity by sildenafil inhibited platelet-derived growth factor-induced phenotype change of VSMCs from a contractile form to a synthetic one. Conversely, the use of cGK inhibitor or gene transfer of dominant-negative cGK reversed the effects of sildenafil, increasing viability of VSMCs and neointimal formation. Interestingly, sildenafil significantly inhibited platelet aggregation induced by ADP or thrombin. This effect was reversed by cGK inhibitor, suggesting that sildenafil inhibits platelet aggregation via cGK pathway. This study demonstrated that sildenafil inhibited neointimal formation and platelet aggregation via cGK pathway. These results suggest that sildenafil could be a promising candidate for drug-eluting stents for the prevention of both restenosis and stent thrombosis. More... »

PAGES

7769

References to SciGraph publications

  • 2001-08. Inhibition of neointimal formation after balloon injury by cilostazol, accompanied by improvement of endothelial dysfunction and induction of hepatocyte growth factor in rat diabetes model in DIABETOLOGIA
  • 2016-11-11. Activation of Protein Kinase G (PKG) Reduces Neointimal Hyperplasia, Inhibits Platelet Aggregation, and Facilitates Re-endothelialization in SCIENTIFIC REPORTS
  • 2015. microRNAs Distinctively Regulate Vascular Smooth Muscle and Endothelial Cells: Functional Implications in Angiogenesis, Atherosclerosis, and In-Stent Restenosis in MICRORNA: BASIC SCIENCE
  • 2002-11. Vascular proliferation and atherosclerosis: New perspectives and therapeutic strategies in NATURE MEDICINE
  • 2010-01-27. PDE5A suppression of acute β-adrenergic activation requires modulation of myocyte beta-3 signaling coupled to PKG-mediated troponin I phosphorylation in BASIC RESEARCH IN CARDIOLOGY
  • 2018-09-10. Cardiovascular stents: overview, evolution, and next generation in PROGRESS IN BIOMATERIALS
  • 2018-09-24. Effects of Cilostazol-Based Triple Antiplatelet Therapy Versus Dual Antiplatelet Therapy After Coronary Drug-Eluting Stent Implantation: An Updated Meta-Analysis of the Randomized Controlled Trials in CLINICAL DRUG INVESTIGATION
  • 2008-02. Sildenafil in DRUGS
  • 2005-01-23. Chronic inhibition of cyclic GMP phosphodiesterase 5A prevents and reverses cardiac hypertrophy in NATURE MEDICINE
  • 2012-11-02. Selective PDE5A inhibition with sildenafil rescues left ventricular dysfunction, inflammatory immune response and cardiac remodeling in angiotensin II-induced heart failure in vivo in BASIC RESEARCH IN CARDIOLOGY
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41598-019-44190-7

    DOI

    http://dx.doi.org/10.1038/s41598-019-44190-7

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1115220655

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/31123275


    Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
    Incoming Citations Browse incoming citations for this publication using opencitations.net

    JSON-LD is the canonical representation for SciGraph data.

    TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

    [
      {
        "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
        "about": [
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/11", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Medical and Health Sciences", 
            "type": "DefinedTerm"
          }, 
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/1102", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Cardiorespiratory Medicine and Haematology", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Angioplasty", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Animals", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Cell Movement", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Cell Proliferation", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Cyclic GMP-Dependent Protein Kinases", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Cyclic Nucleotide Phosphodiesterases, Type 5", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Muscle, Smooth, Vascular", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Myocytes, Smooth Muscle", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Neointima", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Platelet Aggregation", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Rats", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Signal Transduction", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Sildenafil Citrate", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Vascular System Injuries", 
            "type": "DefinedTerm"
          }
        ], 
        "author": [
          {
            "affiliation": {
              "alternateName": "Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea", 
              "id": "http://www.grid.ac/institutes/grid.31501.36", 
              "name": [
                "National Leading Laboratory for Stem Cell Research, Seoul National University College of Medicine, Seoul, Korea", 
                "Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea", 
                "Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Yang", 
            "givenName": "Han-Mo", 
            "id": "sg:person.01101257615.50", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01101257615.50"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea", 
              "id": "http://www.grid.ac/institutes/grid.31501.36", 
              "name": [
                "National Leading Laboratory for Stem Cell Research, Seoul National University College of Medicine, Seoul, Korea", 
                "Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Jin", 
            "givenName": "Sooryeonhwa", 
            "id": "sg:person.01117054302.56", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01117054302.56"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea", 
              "id": "http://www.grid.ac/institutes/grid.31501.36", 
              "name": [
                "National Leading Laboratory for Stem Cell Research, Seoul National University College of Medicine, Seoul, Korea", 
                "Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Jang", 
            "givenName": "Hyunduk", 
            "id": "sg:person.01201614034.71", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01201614034.71"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea", 
              "id": "http://www.grid.ac/institutes/grid.31501.36", 
              "name": [
                "National Leading Laboratory for Stem Cell Research, Seoul National University College of Medicine, Seoul, Korea", 
                "Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Kim", 
            "givenName": "Ju-Young", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea", 
              "id": "http://www.grid.ac/institutes/grid.31501.36", 
              "name": [
                "National Leading Laboratory for Stem Cell Research, Seoul National University College of Medicine, Seoul, Korea", 
                "Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Lee", 
            "givenName": "Joo-Eun", 
            "id": "sg:person.0723732564.37", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0723732564.37"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea", 
              "id": "http://www.grid.ac/institutes/grid.31501.36", 
              "name": [
                "National Leading Laboratory for Stem Cell Research, Seoul National University College of Medicine, Seoul, Korea", 
                "Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Kim", 
            "givenName": "Joonoh", 
            "id": "sg:person.01346114712.12", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01346114712.12"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea", 
              "id": "http://www.grid.ac/institutes/grid.31501.36", 
              "name": [
                "National Leading Laboratory for Stem Cell Research, Seoul National University College of Medicine, Seoul, Korea", 
                "Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea", 
                "Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Kim", 
            "givenName": "Hyo-Soo", 
            "id": "sg:person.010705376560.19", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.010705376560.19"
            ], 
            "type": "Person"
          }
        ], 
        "citation": [
          {
            "id": "sg:pub.10.1007/s00395-012-0308-y", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1010474164", 
              "https://doi.org/10.1007/s00395-012-0308-y"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/978-3-319-22380-3_4", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1017603793", 
              "https://doi.org/10.1007/978-3-319-22380-3_4"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s40261-018-0711-8", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1107213309", 
              "https://doi.org/10.1007/s40261-018-0711-8"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nm1102-1249", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1008205869", 
              "https://doi.org/10.1038/nm1102-1249"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s00395-010-0084-5", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1034132302", 
              "https://doi.org/10.1007/s00395-010-0084-5"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.2165/00003495-200868030-00009", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1012922577", 
              "https://doi.org/10.2165/00003495-200868030-00009"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s001250100593", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1050758046", 
              "https://doi.org/10.1007/s001250100593"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s40204-018-0097-y", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1106905295", 
              "https://doi.org/10.1007/s40204-018-0097-y"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nm1175", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1045090677", 
              "https://doi.org/10.1038/nm1175"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/srep36979", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1010680941", 
              "https://doi.org/10.1038/srep36979"
            ], 
            "type": "CreativeWork"
          }
        ], 
        "datePublished": "2019-05-23", 
        "datePublishedReg": "2019-05-23", 
        "description": "Sildenafil is known to reduce cardiac hypertrophy through cGMP-dependent protein kinase (cGK) activation. Studies have demonstrated that cGK has a central switching role in modulating vascular smooth muscle cell (VSMC) phenotype in response to vascular injury. Here, we aimed to examine the effects of cGK activation by sildenafil on neointimal formation and platelet aggregation. After vascular injury, neointimal hyperplasia in rat carotid arteries was significantly reduced in the sildenafil-treated group. This effect of sildenafil was accompanied by the reduction of viability and migration of VSMCs. Further experiments showed that the increased cGK activity by sildenafil inhibited platelet-derived growth factor-induced phenotype change of VSMCs from a contractile form to a synthetic one. Conversely, the use of cGK inhibitor or gene transfer of dominant-negative cGK reversed the effects of sildenafil, increasing viability of VSMCs and neointimal formation. Interestingly, sildenafil significantly inhibited platelet aggregation induced by ADP or thrombin. This effect was reversed by cGK inhibitor, suggesting that sildenafil inhibits platelet aggregation via cGK pathway. This study demonstrated that sildenafil inhibited neointimal formation and platelet aggregation via cGK pathway. These results suggest that sildenafil could be a promising candidate for drug-eluting stents for the prevention of both restenosis and stent thrombosis.", 
        "genre": "article", 
        "id": "sg:pub.10.1038/s41598-019-44190-7", 
        "inLanguage": "en", 
        "isAccessibleForFree": true, 
        "isPartOf": [
          {
            "id": "sg:journal.1045337", 
            "issn": [
              "2045-2322"
            ], 
            "name": "Scientific Reports", 
            "publisher": "Springer Nature", 
            "type": "Periodical"
          }, 
          {
            "issueNumber": "1", 
            "type": "PublicationIssue"
          }, 
          {
            "type": "PublicationVolume", 
            "volumeNumber": "9"
          }
        ], 
        "keywords": [
          "effect of sildenafil", 
          "neointimal formation", 
          "platelet aggregation", 
          "vascular injury", 
          "neointimal hyperplasia", 
          "sildenafil-treated group", 
          "drug-eluting stents", 
          "rat carotid artery", 
          "vascular smooth muscle cell phenotype", 
          "migration of VSMCs", 
          "smooth muscle cell phenotype", 
          "cGMP-dependent protein kinase activation", 
          "inhibits platelet aggregation", 
          "muscle cell phenotype", 
          "sildenafil inhibits", 
          "stent thrombosis", 
          "carotid artery", 
          "cardiac hypertrophy", 
          "sildenafil", 
          "cGK activation", 
          "protein kinase activation", 
          "contractile form", 
          "cell phenotype", 
          "hyperplasia", 
          "reduction of viability", 
          "phenotype changes", 
          "cGMP-dependent protein kinase", 
          "injury", 
          "VSMC", 
          "activation", 
          "kinase activation", 
          "inhibitors", 
          "cGK inhibitor", 
          "cGK activity", 
          "angioplasty", 
          "thrombosis", 
          "artery", 
          "gene transfer", 
          "restenosis", 
          "hypertrophy", 
          "protein kinase", 
          "pathway", 
          "VSMCs", 
          "stents", 
          "prevention", 
          "Further experiments", 
          "effect", 
          "cGK", 
          "viability", 
          "inhibits", 
          "thrombin", 
          "study", 
          "phenotype", 
          "group", 
          "ADP", 
          "response", 
          "kinase", 
          "activity", 
          "role", 
          "aggregation", 
          "reduction", 
          "migration", 
          "changes", 
          "use", 
          "candidates", 
          "promising candidate", 
          "formation", 
          "results", 
          "synthetic ones", 
          "form", 
          "one", 
          "transfer", 
          "experiments"
        ], 
        "name": "Sildenafil Reduces Neointimal Hyperplasia after Angioplasty and Inhibits Platelet Aggregation via Activation of cGMP-dependent Protein Kinase", 
        "pagination": "7769", 
        "productId": [
          {
            "name": "dimensions_id", 
            "type": "PropertyValue", 
            "value": [
              "pub.1115220655"
            ]
          }, 
          {
            "name": "doi", 
            "type": "PropertyValue", 
            "value": [
              "10.1038/s41598-019-44190-7"
            ]
          }, 
          {
            "name": "pubmed_id", 
            "type": "PropertyValue", 
            "value": [
              "31123275"
            ]
          }
        ], 
        "sameAs": [
          "https://doi.org/10.1038/s41598-019-44190-7", 
          "https://app.dimensions.ai/details/publication/pub.1115220655"
        ], 
        "sdDataset": "articles", 
        "sdDatePublished": "2022-06-01T22:20", 
        "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
        "sdPublisher": {
          "name": "Springer Nature - SN SciGraph project", 
          "type": "Organization"
        }, 
        "sdSource": "s3://com-springernature-scigraph/baseset/20220601/entities/gbq_results/article/article_803.jsonl", 
        "type": "ScholarlyArticle", 
        "url": "https://doi.org/10.1038/s41598-019-44190-7"
      }
    ]
     

    Download the RDF metadata as:  json-ld nt turtle xml License info

    HOW TO GET THIS DATA PROGRAMMATICALLY:

    JSON-LD is a popular format for linked data which is fully compatible with JSON.

    curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/s41598-019-44190-7'

    N-Triples is a line-based linked data format ideal for batch operations.

    curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/s41598-019-44190-7'

    Turtle is a human-readable linked data format.

    curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/s41598-019-44190-7'

    RDF/XML is a standard XML format for linked data.

    curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/s41598-019-44190-7'


     

    This table displays all metadata directly associated to this object as RDF triples.

    273 TRIPLES      22 PREDICATES      123 URIs      105 LITERALS      21 BLANK NODES

    Subject Predicate Object
    1 sg:pub.10.1038/s41598-019-44190-7 schema:about N221d73e11e604059b08198333266bd7d
    2 N4bd574aacf7b4bbfa70718f74cc25dca
    3 N6026942da95b426f92cbcb783dbe44de
    4 N6fd5031990274117a46403a2ff738132
    5 N896b052fc85d4d7e8beaba4d51b17e03
    6 N99971fa1b7af4a5fa11d5dd5f617cfca
    7 Na2a8eca5b0ab4ad5a595749d98a7a639
    8 Nb48de2d06f8d4af3aa0b21ed2cc74082
    9 Nb7a771892d744ca091cf1c4a06d22e98
    10 Ncaccb41999ea40b99f7187293c19dd93
    11 Ncfd8c9aad5d94538a2c77b00c2d97251
    12 Nd3f9c16c749e489184c59efd9bddb484
    13 Nd6e89e86be394896a5ca245579ae162d
    14 Neab80d9647c14f958a5fd07ce8405b51
    15 anzsrc-for:11
    16 anzsrc-for:1102
    17 schema:author Naf1f731d823e4bb28baeb9f9a6675a40
    18 schema:citation sg:pub.10.1007/978-3-319-22380-3_4
    19 sg:pub.10.1007/s001250100593
    20 sg:pub.10.1007/s00395-010-0084-5
    21 sg:pub.10.1007/s00395-012-0308-y
    22 sg:pub.10.1007/s40204-018-0097-y
    23 sg:pub.10.1007/s40261-018-0711-8
    24 sg:pub.10.1038/nm1102-1249
    25 sg:pub.10.1038/nm1175
    26 sg:pub.10.1038/srep36979
    27 sg:pub.10.2165/00003495-200868030-00009
    28 schema:datePublished 2019-05-23
    29 schema:datePublishedReg 2019-05-23
    30 schema:description Sildenafil is known to reduce cardiac hypertrophy through cGMP-dependent protein kinase (cGK) activation. Studies have demonstrated that cGK has a central switching role in modulating vascular smooth muscle cell (VSMC) phenotype in response to vascular injury. Here, we aimed to examine the effects of cGK activation by sildenafil on neointimal formation and platelet aggregation. After vascular injury, neointimal hyperplasia in rat carotid arteries was significantly reduced in the sildenafil-treated group. This effect of sildenafil was accompanied by the reduction of viability and migration of VSMCs. Further experiments showed that the increased cGK activity by sildenafil inhibited platelet-derived growth factor-induced phenotype change of VSMCs from a contractile form to a synthetic one. Conversely, the use of cGK inhibitor or gene transfer of dominant-negative cGK reversed the effects of sildenafil, increasing viability of VSMCs and neointimal formation. Interestingly, sildenafil significantly inhibited platelet aggregation induced by ADP or thrombin. This effect was reversed by cGK inhibitor, suggesting that sildenafil inhibits platelet aggregation via cGK pathway. This study demonstrated that sildenafil inhibited neointimal formation and platelet aggregation via cGK pathway. These results suggest that sildenafil could be a promising candidate for drug-eluting stents for the prevention of both restenosis and stent thrombosis.
    31 schema:genre article
    32 schema:inLanguage en
    33 schema:isAccessibleForFree true
    34 schema:isPartOf N60cd2250640e4b84a67b479673c597bc
    35 Nd45b7437207c496bad26b42e0990ff36
    36 sg:journal.1045337
    37 schema:keywords ADP
    38 Further experiments
    39 VSMC
    40 VSMCs
    41 activation
    42 activity
    43 aggregation
    44 angioplasty
    45 artery
    46 cGK
    47 cGK activation
    48 cGK activity
    49 cGK inhibitor
    50 cGMP-dependent protein kinase
    51 cGMP-dependent protein kinase activation
    52 candidates
    53 cardiac hypertrophy
    54 carotid artery
    55 cell phenotype
    56 changes
    57 contractile form
    58 drug-eluting stents
    59 effect
    60 effect of sildenafil
    61 experiments
    62 form
    63 formation
    64 gene transfer
    65 group
    66 hyperplasia
    67 hypertrophy
    68 inhibitors
    69 inhibits
    70 inhibits platelet aggregation
    71 injury
    72 kinase
    73 kinase activation
    74 migration
    75 migration of VSMCs
    76 muscle cell phenotype
    77 neointimal formation
    78 neointimal hyperplasia
    79 one
    80 pathway
    81 phenotype
    82 phenotype changes
    83 platelet aggregation
    84 prevention
    85 promising candidate
    86 protein kinase
    87 protein kinase activation
    88 rat carotid artery
    89 reduction
    90 reduction of viability
    91 response
    92 restenosis
    93 results
    94 role
    95 sildenafil
    96 sildenafil inhibits
    97 sildenafil-treated group
    98 smooth muscle cell phenotype
    99 stent thrombosis
    100 stents
    101 study
    102 synthetic ones
    103 thrombin
    104 thrombosis
    105 transfer
    106 use
    107 vascular injury
    108 vascular smooth muscle cell phenotype
    109 viability
    110 schema:name Sildenafil Reduces Neointimal Hyperplasia after Angioplasty and Inhibits Platelet Aggregation via Activation of cGMP-dependent Protein Kinase
    111 schema:pagination 7769
    112 schema:productId N7f8cf02421b34ab7ba7f535f9529e21c
    113 N9a03d71b040c4a8c9d3bce31572f95ac
    114 Ned71cb10894e4dbbb8ea7dd68cf0796c
    115 schema:sameAs https://app.dimensions.ai/details/publication/pub.1115220655
    116 https://doi.org/10.1038/s41598-019-44190-7
    117 schema:sdDatePublished 2022-06-01T22:20
    118 schema:sdLicense https://scigraph.springernature.com/explorer/license/
    119 schema:sdPublisher Na37c94c8cd214cd39d67b06121d8b259
    120 schema:url https://doi.org/10.1038/s41598-019-44190-7
    121 sgo:license sg:explorer/license/
    122 sgo:sdDataset articles
    123 rdf:type schema:ScholarlyArticle
    124 N0c7a88c6c6cf4882b93823e5d21e7094 rdf:first sg:person.0723732564.37
    125 rdf:rest N15afcc3fe3d545229ccb8ab904bac497
    126 N15afcc3fe3d545229ccb8ab904bac497 rdf:first sg:person.01346114712.12
    127 rdf:rest N8c1d476f69ee4f06b7e3704c84931eb9
    128 N221d73e11e604059b08198333266bd7d schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    129 schema:name Neointima
    130 rdf:type schema:DefinedTerm
    131 N468bc0d121c249a5b490c0aaea5265e5 rdf:first sg:person.01117054302.56
    132 rdf:rest Nd325b3195520457791755d43f928ecd7
    133 N4bd574aacf7b4bbfa70718f74cc25dca schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    134 schema:name Angioplasty
    135 rdf:type schema:DefinedTerm
    136 N6026942da95b426f92cbcb783dbe44de schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    137 schema:name Platelet Aggregation
    138 rdf:type schema:DefinedTerm
    139 N60cd2250640e4b84a67b479673c597bc schema:volumeNumber 9
    140 rdf:type schema:PublicationVolume
    141 N6fd5031990274117a46403a2ff738132 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    142 schema:name Animals
    143 rdf:type schema:DefinedTerm
    144 N7f8cf02421b34ab7ba7f535f9529e21c schema:name pubmed_id
    145 schema:value 31123275
    146 rdf:type schema:PropertyValue
    147 N896b052fc85d4d7e8beaba4d51b17e03 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    148 schema:name Rats
    149 rdf:type schema:DefinedTerm
    150 N8c1d476f69ee4f06b7e3704c84931eb9 rdf:first sg:person.010705376560.19
    151 rdf:rest rdf:nil
    152 N99971fa1b7af4a5fa11d5dd5f617cfca schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    153 schema:name Cell Proliferation
    154 rdf:type schema:DefinedTerm
    155 N9a03d71b040c4a8c9d3bce31572f95ac schema:name dimensions_id
    156 schema:value pub.1115220655
    157 rdf:type schema:PropertyValue
    158 Na133e68dd7584d16885b57c054756179 rdf:first Nc6f6aa0432564e9992df00ca600dc054
    159 rdf:rest N0c7a88c6c6cf4882b93823e5d21e7094
    160 Na2a8eca5b0ab4ad5a595749d98a7a639 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    161 schema:name Muscle, Smooth, Vascular
    162 rdf:type schema:DefinedTerm
    163 Na37c94c8cd214cd39d67b06121d8b259 schema:name Springer Nature - SN SciGraph project
    164 rdf:type schema:Organization
    165 Naf1f731d823e4bb28baeb9f9a6675a40 rdf:first sg:person.01101257615.50
    166 rdf:rest N468bc0d121c249a5b490c0aaea5265e5
    167 Nb48de2d06f8d4af3aa0b21ed2cc74082 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    168 schema:name Vascular System Injuries
    169 rdf:type schema:DefinedTerm
    170 Nb7a771892d744ca091cf1c4a06d22e98 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    171 schema:name Myocytes, Smooth Muscle
    172 rdf:type schema:DefinedTerm
    173 Nc6f6aa0432564e9992df00ca600dc054 schema:affiliation grid-institutes:grid.31501.36
    174 schema:familyName Kim
    175 schema:givenName Ju-Young
    176 rdf:type schema:Person
    177 Ncaccb41999ea40b99f7187293c19dd93 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    178 schema:name Cyclic Nucleotide Phosphodiesterases, Type 5
    179 rdf:type schema:DefinedTerm
    180 Ncfd8c9aad5d94538a2c77b00c2d97251 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    181 schema:name Signal Transduction
    182 rdf:type schema:DefinedTerm
    183 Nd325b3195520457791755d43f928ecd7 rdf:first sg:person.01201614034.71
    184 rdf:rest Na133e68dd7584d16885b57c054756179
    185 Nd3f9c16c749e489184c59efd9bddb484 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    186 schema:name Sildenafil Citrate
    187 rdf:type schema:DefinedTerm
    188 Nd45b7437207c496bad26b42e0990ff36 schema:issueNumber 1
    189 rdf:type schema:PublicationIssue
    190 Nd6e89e86be394896a5ca245579ae162d schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    191 schema:name Cyclic GMP-Dependent Protein Kinases
    192 rdf:type schema:DefinedTerm
    193 Neab80d9647c14f958a5fd07ce8405b51 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    194 schema:name Cell Movement
    195 rdf:type schema:DefinedTerm
    196 Ned71cb10894e4dbbb8ea7dd68cf0796c schema:name doi
    197 schema:value 10.1038/s41598-019-44190-7
    198 rdf:type schema:PropertyValue
    199 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
    200 schema:name Medical and Health Sciences
    201 rdf:type schema:DefinedTerm
    202 anzsrc-for:1102 schema:inDefinedTermSet anzsrc-for:
    203 schema:name Cardiorespiratory Medicine and Haematology
    204 rdf:type schema:DefinedTerm
    205 sg:journal.1045337 schema:issn 2045-2322
    206 schema:name Scientific Reports
    207 schema:publisher Springer Nature
    208 rdf:type schema:Periodical
    209 sg:person.010705376560.19 schema:affiliation grid-institutes:grid.31501.36
    210 schema:familyName Kim
    211 schema:givenName Hyo-Soo
    212 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.010705376560.19
    213 rdf:type schema:Person
    214 sg:person.01101257615.50 schema:affiliation grid-institutes:grid.31501.36
    215 schema:familyName Yang
    216 schema:givenName Han-Mo
    217 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01101257615.50
    218 rdf:type schema:Person
    219 sg:person.01117054302.56 schema:affiliation grid-institutes:grid.31501.36
    220 schema:familyName Jin
    221 schema:givenName Sooryeonhwa
    222 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01117054302.56
    223 rdf:type schema:Person
    224 sg:person.01201614034.71 schema:affiliation grid-institutes:grid.31501.36
    225 schema:familyName Jang
    226 schema:givenName Hyunduk
    227 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01201614034.71
    228 rdf:type schema:Person
    229 sg:person.01346114712.12 schema:affiliation grid-institutes:grid.31501.36
    230 schema:familyName Kim
    231 schema:givenName Joonoh
    232 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01346114712.12
    233 rdf:type schema:Person
    234 sg:person.0723732564.37 schema:affiliation grid-institutes:grid.31501.36
    235 schema:familyName Lee
    236 schema:givenName Joo-Eun
    237 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0723732564.37
    238 rdf:type schema:Person
    239 sg:pub.10.1007/978-3-319-22380-3_4 schema:sameAs https://app.dimensions.ai/details/publication/pub.1017603793
    240 https://doi.org/10.1007/978-3-319-22380-3_4
    241 rdf:type schema:CreativeWork
    242 sg:pub.10.1007/s001250100593 schema:sameAs https://app.dimensions.ai/details/publication/pub.1050758046
    243 https://doi.org/10.1007/s001250100593
    244 rdf:type schema:CreativeWork
    245 sg:pub.10.1007/s00395-010-0084-5 schema:sameAs https://app.dimensions.ai/details/publication/pub.1034132302
    246 https://doi.org/10.1007/s00395-010-0084-5
    247 rdf:type schema:CreativeWork
    248 sg:pub.10.1007/s00395-012-0308-y schema:sameAs https://app.dimensions.ai/details/publication/pub.1010474164
    249 https://doi.org/10.1007/s00395-012-0308-y
    250 rdf:type schema:CreativeWork
    251 sg:pub.10.1007/s40204-018-0097-y schema:sameAs https://app.dimensions.ai/details/publication/pub.1106905295
    252 https://doi.org/10.1007/s40204-018-0097-y
    253 rdf:type schema:CreativeWork
    254 sg:pub.10.1007/s40261-018-0711-8 schema:sameAs https://app.dimensions.ai/details/publication/pub.1107213309
    255 https://doi.org/10.1007/s40261-018-0711-8
    256 rdf:type schema:CreativeWork
    257 sg:pub.10.1038/nm1102-1249 schema:sameAs https://app.dimensions.ai/details/publication/pub.1008205869
    258 https://doi.org/10.1038/nm1102-1249
    259 rdf:type schema:CreativeWork
    260 sg:pub.10.1038/nm1175 schema:sameAs https://app.dimensions.ai/details/publication/pub.1045090677
    261 https://doi.org/10.1038/nm1175
    262 rdf:type schema:CreativeWork
    263 sg:pub.10.1038/srep36979 schema:sameAs https://app.dimensions.ai/details/publication/pub.1010680941
    264 https://doi.org/10.1038/srep36979
    265 rdf:type schema:CreativeWork
    266 sg:pub.10.2165/00003495-200868030-00009 schema:sameAs https://app.dimensions.ai/details/publication/pub.1012922577
    267 https://doi.org/10.2165/00003495-200868030-00009
    268 rdf:type schema:CreativeWork
    269 grid-institutes:grid.31501.36 schema:alternateName Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea
    270 schema:name Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
    271 Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea
    272 National Leading Laboratory for Stem Cell Research, Seoul National University College of Medicine, Seoul, Korea
    273 rdf:type schema:Organization
     




    Preview window. Press ESC to close (or click here)


    ...