PPARγ modulates vascular smooth muscle cell phenotype via a protein kinase G-dependent pathway and reduces neointimal hyperplasia after vascular injury View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2013-11-29

AUTHORS

Han-Mo Yang, Baek-Kyung Kim, Ju-Young Kim, Yoo-Wook Kwon, Sooryeonhwa Jin, Joo-Eun Lee, Hyun-Jai Cho, Hae-Young Lee, Hyun-Jae Kang, Byung-Hee Oh, Young-Bae Park, Hyo-Soo Kim

ABSTRACT

Vascular smooth muscle cells (VSMCs) undergo phenotypic changes in response to vascular injury such as angioplasty. Protein kinase G (PKG) has an important role in the process of VSMC phenotype switching. In this study, we examined whether rosiglitazone, a peroxisome proliferator-activated receptor (PPAR)-γ agonist, could modulate VSMC phenotype through the PKG pathway to reduce neointimal hyperplasia after angioplasty. In vitro experiments showed that rosiglitazone inhibited the phenotype change of VSMCs from a contractile to a synthetic form. The platelet-derived growth factor (PDGF)-induced reduction of PKG level was reversed by rosiglitazone treatment, resulting in increased PKG activity. This increased activity of PKG resulted in phosphorylation of vasodilator-stimulated phosphoprotein at serine 239, leading to inhibited proliferation of VSMCs. Interestingly, rosiglitazone did not change the level of nitric oxide (NO) or cyclic guanosine monophosphate (cGMP), which are upstream of PKG, suggesting that rosiglitazone influences PKG itself. Chromatin immunoprecipitation assays for the PKG promoter showed that the activation of PKG by rosiglitazone was mediated by the increased binding of Sp1 on the promoter region of PKG. In vivo experiments showed that rosiglitazone significantly inhibited neointimal formation after balloon injury. Immunohistochemistry staining for calponin and thrombospondin showed that this effect of rosiglitazone was mediated by modulating VSMC phenotype. Our findings demonstrate that rosiglitazone is a potent modulator of VSMC phenotype, which is regulated by PKG. This activation of PKG by rosiglitazone results in reduced neointimal hyperplasia after angioplasty. These results provide important mechanistic insight into the cardiovascular-protective effect of PPARγ. More... »

PAGES

e65-e65

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/emm.2013.112

DOI

http://dx.doi.org/10.1038/emm.2013.112

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1004651461

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/24287871


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/2008/03", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Chemical Sciences", 
        "type": "DefinedTerm"
      }, 
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/0304", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Medicinal and Biomolecular Chemistry", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Animals", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Aorta", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Calcium-Binding Proteins", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Cell Proliferation", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Cyclic GMP", 
        "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": "Hyperplasia", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Microfilament Proteins", 
        "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": "Nitric Oxide", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "PPAR gamma", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Promoter Regions, Genetic", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Rats", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Rats, Sprague-Dawley", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Rosiglitazone", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Sp1 Transcription Factor", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Thiazolidinediones", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Thrombospondins", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Tunica Intima", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Vascular System Injuries", 
        "type": "DefinedTerm"
      }
    ], 
    "author": [
      {
        "affiliation": {
          "alternateName": "Innovative Research Institute for Cell Therapy, Seoul National University Hospital, Seoul, Korea", 
          "id": "http://www.grid.ac/institutes/grid.412484.f", 
          "name": [
            "National Research Laboratory for Stem Cell Niche, Seoul National University College of Medicine, Seoul, Korea", 
            "Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea", 
            "Innovative Research Institute for Cell Therapy, Seoul National University Hospital, 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": "Innovative Research Institute for Cell Therapy, Seoul National University Hospital, Seoul, Korea", 
          "id": "http://www.grid.ac/institutes/grid.412484.f", 
          "name": [
            "National Research Laboratory for Stem Cell Niche, Seoul National University College of Medicine, Seoul, Korea", 
            "Innovative Research Institute for Cell Therapy, Seoul National University Hospital, Seoul, Korea"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Kim", 
        "givenName": "Baek-Kyung", 
        "id": "sg:person.01357663360.74", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01357663360.74"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Innovative Research Institute for Cell Therapy, Seoul National University Hospital, Seoul, Korea", 
          "id": "http://www.grid.ac/institutes/grid.412484.f", 
          "name": [
            "National Research Laboratory for Stem Cell Niche, Seoul National University College of Medicine, Seoul, Korea", 
            "Innovative Research Institute for Cell Therapy, Seoul National University Hospital, Seoul, Korea"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Kim", 
        "givenName": "Ju-Young", 
        "id": "sg:person.01250553160.10", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01250553160.10"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Innovative Research Institute for Cell Therapy, Seoul National University Hospital, Seoul, Korea", 
          "id": "http://www.grid.ac/institutes/grid.412484.f", 
          "name": [
            "National Research Laboratory for Stem Cell Niche, Seoul National University College of Medicine, Seoul, Korea", 
            "Innovative Research Institute for Cell Therapy, Seoul National University Hospital, Seoul, Korea"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Kwon", 
        "givenName": "Yoo-Wook", 
        "id": "sg:person.01246601246.27", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01246601246.27"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Innovative Research Institute for Cell Therapy, Seoul National University Hospital, Seoul, Korea", 
          "id": "http://www.grid.ac/institutes/grid.412484.f", 
          "name": [
            "National Research Laboratory for Stem Cell Niche, Seoul National University College of Medicine, Seoul, Korea", 
            "Innovative Research Institute for Cell Therapy, Seoul National University Hospital, 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": "Innovative Research Institute for Cell Therapy, Seoul National University Hospital, Seoul, Korea", 
          "id": "http://www.grid.ac/institutes/grid.412484.f", 
          "name": [
            "National Research Laboratory for Stem Cell Niche, Seoul National University College of Medicine, Seoul, Korea", 
            "Innovative Research Institute for Cell Therapy, Seoul National University Hospital, 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": "Innovative Research Institute for Cell Therapy, Seoul National University Hospital, Seoul, Korea", 
          "id": "http://www.grid.ac/institutes/grid.412484.f", 
          "name": [
            "National Research Laboratory for Stem Cell Niche, Seoul National University College of Medicine, Seoul, Korea", 
            "Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea", 
            "Innovative Research Institute for Cell Therapy, Seoul National University Hospital, Seoul, Korea"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Cho", 
        "givenName": "Hyun-Jai", 
        "id": "sg:person.01300017742.41", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01300017742.41"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Innovative Research Institute for Cell Therapy, Seoul National University Hospital, Seoul, Korea", 
          "id": "http://www.grid.ac/institutes/grid.412484.f", 
          "name": [
            "National Research Laboratory for Stem Cell Niche, Seoul National University College of Medicine, Seoul, Korea", 
            "Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea", 
            "Innovative Research Institute for Cell Therapy, Seoul National University Hospital, Seoul, Korea"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Lee", 
        "givenName": "Hae-Young", 
        "id": "sg:person.01147373015.99", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01147373015.99"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Innovative Research Institute for Cell Therapy, Seoul National University Hospital, Seoul, Korea", 
          "id": "http://www.grid.ac/institutes/grid.412484.f", 
          "name": [
            "National Research Laboratory for Stem Cell Niche, Seoul National University College of Medicine, Seoul, Korea", 
            "Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea", 
            "Innovative Research Institute for Cell Therapy, Seoul National University Hospital, Seoul, Korea"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Kang", 
        "givenName": "Hyun-Jae", 
        "id": "sg:person.01254550333.69", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01254550333.69"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Innovative Research Institute for Cell Therapy, Seoul National University Hospital, Seoul, Korea", 
          "id": "http://www.grid.ac/institutes/grid.412484.f", 
          "name": [
            "National Research Laboratory for Stem Cell Niche, Seoul National University College of Medicine, Seoul, Korea", 
            "Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea", 
            "Innovative Research Institute for Cell Therapy, Seoul National University Hospital, Seoul, Korea"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Oh", 
        "givenName": "Byung-Hee", 
        "id": "sg:person.01132635714.61", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01132635714.61"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Innovative Research Institute for Cell Therapy, Seoul National University Hospital, Seoul, Korea", 
          "id": "http://www.grid.ac/institutes/grid.412484.f", 
          "name": [
            "National Research Laboratory for Stem Cell Niche, Seoul National University College of Medicine, Seoul, Korea", 
            "Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea", 
            "Innovative Research Institute for Cell Therapy, Seoul National University Hospital, Seoul, Korea"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Park", 
        "givenName": "Young-Bae", 
        "id": "sg:person.0661601052.43", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0661601052.43"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Molecular Medicine and Biopharmaceutical Sciences, Seoul National University, Seoul, Korea", 
          "id": "http://www.grid.ac/institutes/grid.31501.36", 
          "name": [
            "National Research Laboratory for Stem Cell Niche, Seoul National University College of Medicine, Seoul, Korea", 
            "Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea", 
            "Innovative Research Institute for Cell Therapy, Seoul National University Hospital, Seoul, Korea", 
            "Molecular Medicine and Biopharmaceutical Sciences, 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.10.1038/nm1175", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1045090677", 
          "https://doi.org/10.1038/nm1175"
        ], 
        "type": "CreativeWork"
      }
    ], 
    "datePublished": "2013-11-29", 
    "datePublishedReg": "2013-11-29", 
    "description": "Vascular smooth muscle cells (VSMCs) undergo phenotypic changes in response to vascular injury such as angioplasty. Protein kinase G (PKG) has an important role in the process of VSMC phenotype switching. In this study, we examined whether rosiglitazone, a peroxisome proliferator-activated receptor (PPAR)-\u03b3 agonist, could modulate VSMC phenotype through the PKG pathway to reduce neointimal hyperplasia after angioplasty. In vitro experiments showed that rosiglitazone inhibited the phenotype change of VSMCs from a contractile to a synthetic form. The platelet-derived growth factor (PDGF)-induced reduction of PKG level was reversed by rosiglitazone treatment, resulting in increased PKG activity. This increased activity of PKG resulted in phosphorylation of vasodilator-stimulated phosphoprotein at serine 239, leading to inhibited proliferation of VSMCs. Interestingly, rosiglitazone did not change the level of nitric oxide (NO) or cyclic guanosine monophosphate (cGMP), which are upstream of PKG, suggesting that rosiglitazone influences PKG itself. Chromatin immunoprecipitation assays for the PKG promoter showed that the activation of PKG by rosiglitazone was mediated by the increased binding of Sp1 on the promoter region of PKG. In vivo experiments showed that rosiglitazone significantly inhibited neointimal formation after balloon injury. Immunohistochemistry staining for calponin and thrombospondin showed that this effect of rosiglitazone was mediated by modulating VSMC phenotype. Our findings demonstrate that rosiglitazone is a potent modulator of VSMC phenotype, which is regulated by PKG. This activation of PKG by rosiglitazone results in reduced neointimal hyperplasia after angioplasty. These results provide important mechanistic insight into the cardiovascular-protective effect of PPAR\u03b3.", 
    "genre": "article", 
    "id": "sg:pub.10.1038/emm.2013.112", 
    "inLanguage": "en", 
    "isAccessibleForFree": true, 
    "isPartOf": [
      {
        "id": "sg:journal.1085098", 
        "issn": [
          "1226-3613", 
          "2092-6413"
        ], 
        "name": "Experimental & Molecular Medicine", 
        "publisher": "Springer Nature", 
        "type": "Periodical"
      }, 
      {
        "issueNumber": "11", 
        "type": "PublicationIssue"
      }, 
      {
        "type": "PublicationVolume", 
        "volumeNumber": "45"
      }
    ], 
    "keywords": [
      "vascular smooth muscle cells", 
      "protein kinase G", 
      "cyclic guanosine monophosphate", 
      "neointimal hyperplasia", 
      "activation of PKG", 
      "VSMC phenotype", 
      "vascular injury", 
      "nitric oxide", 
      "peroxisome proliferator-activated receptor", 
      "cardiovascular protective effects", 
      "effects of rosiglitazone", 
      "kinase G", 
      "proliferator-activated receptor", 
      "platelet-derived growth factor", 
      "vascular smooth muscle cell phenotype", 
      "smooth muscle cell phenotype", 
      "smooth muscle cells", 
      "muscle cell phenotype", 
      "VSMC phenotype switching", 
      "balloon injury", 
      "rosiglitazone treatment", 
      "neointimal formation", 
      "\u03b3 agonist", 
      "PKG pathway", 
      "rosiglitazone", 
      "inhibited proliferation", 
      "angioplasty", 
      "vasodilator-stimulated phosphoprotein", 
      "potent modulator", 
      "muscle cells", 
      "PKG levels", 
      "hyperplasia", 
      "growth factor", 
      "injury", 
      "guanosine monophosphate", 
      "PKG activity", 
      "cell phenotype", 
      "dependent pathway", 
      "phenotype switching", 
      "phenotype changes", 
      "vivo experiments", 
      "serine 239", 
      "PPAR\u03b3", 
      "phenotype", 
      "phenotypic changes", 
      "important mechanistic insights", 
      "activation", 
      "synthetic form", 
      "chromatin immunoprecipitation", 
      "agonists", 
      "immunohistochemistry", 
      "promoter region", 
      "pathway", 
      "contractile", 
      "important role", 
      "receptors", 
      "binding of Sp1", 
      "calponin", 
      "levels", 
      "treatment", 
      "mechanistic insights", 
      "activity", 
      "proliferation", 
      "thrombospondin", 
      "effect", 
      "cells", 
      "monophosphate", 
      "changes", 
      "immunoprecipitation", 
      "phosphorylation", 
      "findings", 
      "response", 
      "modulator", 
      "factors", 
      "study", 
      "role", 
      "binding", 
      "reduction", 
      "promoter", 
      "results", 
      "phosphoprotein", 
      "Sp1", 
      "region", 
      "insights", 
      "form", 
      "formation", 
      "experiments", 
      "oxide", 
      "process", 
      "switching"
    ], 
    "name": "PPAR\u03b3 modulates vascular smooth muscle cell phenotype via a protein kinase G-dependent pathway and reduces neointimal hyperplasia after vascular injury", 
    "pagination": "e65-e65", 
    "productId": [
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1004651461"
        ]
      }, 
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1038/emm.2013.112"
        ]
      }, 
      {
        "name": "pubmed_id", 
        "type": "PropertyValue", 
        "value": [
          "24287871"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1038/emm.2013.112", 
      "https://app.dimensions.ai/details/publication/pub.1004651461"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2022-05-20T07:29", 
    "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
    "sdPublisher": {
      "name": "Springer Nature - SN SciGraph project", 
      "type": "Organization"
    }, 
    "sdSource": "s3://com-springernature-scigraph/baseset/20220519/entities/gbq_results/article/article_602.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "https://doi.org/10.1038/emm.2013.112"
  }
]
 

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/emm.2013.112'

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/emm.2013.112'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/emm.2013.112'

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

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/emm.2013.112'


 

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

325 TRIPLES      22 PREDICATES      138 URIs      129 LITERALS      28 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1038/emm.2013.112 schema:about N040149cad0624752b094ba5b8a719e17
2 N092c253e645740739408328ff912b931
3 N11d97670874644b3885653ed58b90807
4 N1d385d3383c84d2895be9010134b7849
5 N2899ae0a02e74e3a8566b6598b64d987
6 N2f01cc1f0e264404b5b3f86b5b2712b0
7 N3322ca2a53fc4baeadbb82b09b6559f9
8 N595939c28ab443889cb77ae329173b31
9 N598e012ece1d451d863a177d4ae7c175
10 N59adb2af398041fbb72b02401734529a
11 N633b7ea4ab6b4ed381e3927d0ed15df2
12 N6fe0dcca738d4e019b6b4560e82d414a
13 N9d04861c2c614de7822f3286d162de81
14 Nb607759c07684989b888e79151056a20
15 Nbc1e70761db0410b89565561d27f03db
16 Ndd5be11294e44f8cbd1da0cd445b0621
17 Nddb6e8d4fabe499984954360602e1d26
18 Nea9ed2e6a29a45e1a737316545612a01
19 Necab9cfe665b4762a20c66b29c34ddbd
20 Nfba4c1dc2ecd438c9800003b97511904
21 Nfc1e3425584d4e1a92051c0216544258
22 anzsrc-for:03
23 anzsrc-for:0304
24 schema:author Neefa7da6f3b04f4c82862f0a204d05bc
25 schema:citation sg:pub.10.1038/nm1175
26 schema:datePublished 2013-11-29
27 schema:datePublishedReg 2013-11-29
28 schema:description Vascular smooth muscle cells (VSMCs) undergo phenotypic changes in response to vascular injury such as angioplasty. Protein kinase G (PKG) has an important role in the process of VSMC phenotype switching. In this study, we examined whether rosiglitazone, a peroxisome proliferator-activated receptor (PPAR)-γ agonist, could modulate VSMC phenotype through the PKG pathway to reduce neointimal hyperplasia after angioplasty. In vitro experiments showed that rosiglitazone inhibited the phenotype change of VSMCs from a contractile to a synthetic form. The platelet-derived growth factor (PDGF)-induced reduction of PKG level was reversed by rosiglitazone treatment, resulting in increased PKG activity. This increased activity of PKG resulted in phosphorylation of vasodilator-stimulated phosphoprotein at serine 239, leading to inhibited proliferation of VSMCs. Interestingly, rosiglitazone did not change the level of nitric oxide (NO) or cyclic guanosine monophosphate (cGMP), which are upstream of PKG, suggesting that rosiglitazone influences PKG itself. Chromatin immunoprecipitation assays for the PKG promoter showed that the activation of PKG by rosiglitazone was mediated by the increased binding of Sp1 on the promoter region of PKG. In vivo experiments showed that rosiglitazone significantly inhibited neointimal formation after balloon injury. Immunohistochemistry staining for calponin and thrombospondin showed that this effect of rosiglitazone was mediated by modulating VSMC phenotype. Our findings demonstrate that rosiglitazone is a potent modulator of VSMC phenotype, which is regulated by PKG. This activation of PKG by rosiglitazone results in reduced neointimal hyperplasia after angioplasty. These results provide important mechanistic insight into the cardiovascular-protective effect of PPARγ.
29 schema:genre article
30 schema:inLanguage en
31 schema:isAccessibleForFree true
32 schema:isPartOf N1ce564b6ed0a49598a927dfb72ceb8a0
33 N374a711555ad4d54ad2d342638243dbd
34 sg:journal.1085098
35 schema:keywords PKG activity
36 PKG levels
37 PKG pathway
38 PPARγ
39 Sp1
40 VSMC phenotype
41 VSMC phenotype switching
42 activation
43 activation of PKG
44 activity
45 agonists
46 angioplasty
47 balloon injury
48 binding
49 binding of Sp1
50 calponin
51 cardiovascular protective effects
52 cell phenotype
53 cells
54 changes
55 chromatin immunoprecipitation
56 contractile
57 cyclic guanosine monophosphate
58 dependent pathway
59 effect
60 effects of rosiglitazone
61 experiments
62 factors
63 findings
64 form
65 formation
66 growth factor
67 guanosine monophosphate
68 hyperplasia
69 immunohistochemistry
70 immunoprecipitation
71 important mechanistic insights
72 important role
73 inhibited proliferation
74 injury
75 insights
76 kinase G
77 levels
78 mechanistic insights
79 modulator
80 monophosphate
81 muscle cell phenotype
82 muscle cells
83 neointimal formation
84 neointimal hyperplasia
85 nitric oxide
86 oxide
87 pathway
88 peroxisome proliferator-activated receptor
89 phenotype
90 phenotype changes
91 phenotype switching
92 phenotypic changes
93 phosphoprotein
94 phosphorylation
95 platelet-derived growth factor
96 potent modulator
97 process
98 proliferation
99 proliferator-activated receptor
100 promoter
101 promoter region
102 protein kinase G
103 receptors
104 reduction
105 region
106 response
107 results
108 role
109 rosiglitazone
110 rosiglitazone treatment
111 serine 239
112 smooth muscle cell phenotype
113 smooth muscle cells
114 study
115 switching
116 synthetic form
117 thrombospondin
118 treatment
119 vascular injury
120 vascular smooth muscle cell phenotype
121 vascular smooth muscle cells
122 vasodilator-stimulated phosphoprotein
123 vivo experiments
124 γ agonist
125 schema:name PPARγ modulates vascular smooth muscle cell phenotype via a protein kinase G-dependent pathway and reduces neointimal hyperplasia after vascular injury
126 schema:pagination e65-e65
127 schema:productId N2c2889ccb9d84974b33393c259a6998b
128 Ncea1f0d16e544833b449bc844794f4b6
129 Nf07656d7ec3a4890876edc7674909b79
130 schema:sameAs https://app.dimensions.ai/details/publication/pub.1004651461
131 https://doi.org/10.1038/emm.2013.112
132 schema:sdDatePublished 2022-05-20T07:29
133 schema:sdLicense https://scigraph.springernature.com/explorer/license/
134 schema:sdPublisher N5de5708fcde54d3fa829733af9286bc8
135 schema:url https://doi.org/10.1038/emm.2013.112
136 sgo:license sg:explorer/license/
137 sgo:sdDataset articles
138 rdf:type schema:ScholarlyArticle
139 N040149cad0624752b094ba5b8a719e17 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
140 schema:name Tunica Intima
141 rdf:type schema:DefinedTerm
142 N092c253e645740739408328ff912b931 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
143 schema:name Rats
144 rdf:type schema:DefinedTerm
145 N1070aec9172b4021ace206165050ab05 rdf:first sg:person.0661601052.43
146 rdf:rest N69535eca116342fc9e4916627101277e
147 N11d97670874644b3885653ed58b90807 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
148 schema:name Cell Proliferation
149 rdf:type schema:DefinedTerm
150 N1ce564b6ed0a49598a927dfb72ceb8a0 schema:volumeNumber 45
151 rdf:type schema:PublicationVolume
152 N1d385d3383c84d2895be9010134b7849 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
153 schema:name Microfilament Proteins
154 rdf:type schema:DefinedTerm
155 N2899ae0a02e74e3a8566b6598b64d987 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
156 schema:name Myocytes, Smooth Muscle
157 rdf:type schema:DefinedTerm
158 N2c2889ccb9d84974b33393c259a6998b schema:name doi
159 schema:value 10.1038/emm.2013.112
160 rdf:type schema:PropertyValue
161 N2f01cc1f0e264404b5b3f86b5b2712b0 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
162 schema:name Nitric Oxide
163 rdf:type schema:DefinedTerm
164 N3322ca2a53fc4baeadbb82b09b6559f9 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
165 schema:name Cyclic GMP
166 rdf:type schema:DefinedTerm
167 N374a711555ad4d54ad2d342638243dbd schema:issueNumber 11
168 rdf:type schema:PublicationIssue
169 N4c1c29a91999480190fee54dad378426 rdf:first sg:person.01132635714.61
170 rdf:rest N1070aec9172b4021ace206165050ab05
171 N595939c28ab443889cb77ae329173b31 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
172 schema:name Aorta
173 rdf:type schema:DefinedTerm
174 N598e012ece1d451d863a177d4ae7c175 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
175 schema:name Cyclic GMP-Dependent Protein Kinases
176 rdf:type schema:DefinedTerm
177 N59adb2af398041fbb72b02401734529a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
178 schema:name Thiazolidinediones
179 rdf:type schema:DefinedTerm
180 N5de5708fcde54d3fa829733af9286bc8 schema:name Springer Nature - SN SciGraph project
181 rdf:type schema:Organization
182 N5e872128376648f782c8be0dd273ce06 rdf:first sg:person.01250553160.10
183 rdf:rest Nd18476e8a70141d392d2807cdd260322
184 N633b7ea4ab6b4ed381e3927d0ed15df2 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
185 schema:name PPAR gamma
186 rdf:type schema:DefinedTerm
187 N69535eca116342fc9e4916627101277e rdf:first sg:person.010705376560.19
188 rdf:rest rdf:nil
189 N6fe0dcca738d4e019b6b4560e82d414a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
190 schema:name Animals
191 rdf:type schema:DefinedTerm
192 N792e53ce52ef408f9b861608927bae2d rdf:first sg:person.0723732564.37
193 rdf:rest Nadb313305bc24fe196b4873a80fd71da
194 N7f73dac5af7c42b8bd0c9bbf4d1ba920 rdf:first sg:person.01357663360.74
195 rdf:rest N5e872128376648f782c8be0dd273ce06
196 N91d93f2b4f434c5fb86ea076721a0a33 rdf:first sg:person.01254550333.69
197 rdf:rest N4c1c29a91999480190fee54dad378426
198 N9441e62693044c74a3b3908795974f0e rdf:first sg:person.01117054302.56
199 rdf:rest N792e53ce52ef408f9b861608927bae2d
200 N9d04861c2c614de7822f3286d162de81 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
201 schema:name Promoter Regions, Genetic
202 rdf:type schema:DefinedTerm
203 Nadb313305bc24fe196b4873a80fd71da rdf:first sg:person.01300017742.41
204 rdf:rest Nb3f15228fcc5457ca7d55072d20295f6
205 Nb3f15228fcc5457ca7d55072d20295f6 rdf:first sg:person.01147373015.99
206 rdf:rest N91d93f2b4f434c5fb86ea076721a0a33
207 Nb607759c07684989b888e79151056a20 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
208 schema:name Hyperplasia
209 rdf:type schema:DefinedTerm
210 Nbc1e70761db0410b89565561d27f03db schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
211 schema:name Calcium-Binding Proteins
212 rdf:type schema:DefinedTerm
213 Ncea1f0d16e544833b449bc844794f4b6 schema:name pubmed_id
214 schema:value 24287871
215 rdf:type schema:PropertyValue
216 Nd18476e8a70141d392d2807cdd260322 rdf:first sg:person.01246601246.27
217 rdf:rest N9441e62693044c74a3b3908795974f0e
218 Ndd5be11294e44f8cbd1da0cd445b0621 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
219 schema:name Rosiglitazone
220 rdf:type schema:DefinedTerm
221 Nddb6e8d4fabe499984954360602e1d26 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
222 schema:name Thrombospondins
223 rdf:type schema:DefinedTerm
224 Nea9ed2e6a29a45e1a737316545612a01 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
225 schema:name Muscle, Smooth, Vascular
226 rdf:type schema:DefinedTerm
227 Necab9cfe665b4762a20c66b29c34ddbd schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
228 schema:name Rats, Sprague-Dawley
229 rdf:type schema:DefinedTerm
230 Neefa7da6f3b04f4c82862f0a204d05bc rdf:first sg:person.01101257615.50
231 rdf:rest N7f73dac5af7c42b8bd0c9bbf4d1ba920
232 Nf07656d7ec3a4890876edc7674909b79 schema:name dimensions_id
233 schema:value pub.1004651461
234 rdf:type schema:PropertyValue
235 Nfba4c1dc2ecd438c9800003b97511904 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
236 schema:name Vascular System Injuries
237 rdf:type schema:DefinedTerm
238 Nfc1e3425584d4e1a92051c0216544258 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
239 schema:name Sp1 Transcription Factor
240 rdf:type schema:DefinedTerm
241 anzsrc-for:03 schema:inDefinedTermSet anzsrc-for:
242 schema:name Chemical Sciences
243 rdf:type schema:DefinedTerm
244 anzsrc-for:0304 schema:inDefinedTermSet anzsrc-for:
245 schema:name Medicinal and Biomolecular Chemistry
246 rdf:type schema:DefinedTerm
247 sg:journal.1085098 schema:issn 1226-3613
248 2092-6413
249 schema:name Experimental & Molecular Medicine
250 schema:publisher Springer Nature
251 rdf:type schema:Periodical
252 sg:person.010705376560.19 schema:affiliation grid-institutes:grid.31501.36
253 schema:familyName Kim
254 schema:givenName Hyo-Soo
255 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.010705376560.19
256 rdf:type schema:Person
257 sg:person.01101257615.50 schema:affiliation grid-institutes:grid.412484.f
258 schema:familyName Yang
259 schema:givenName Han-Mo
260 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01101257615.50
261 rdf:type schema:Person
262 sg:person.01117054302.56 schema:affiliation grid-institutes:grid.412484.f
263 schema:familyName Jin
264 schema:givenName Sooryeonhwa
265 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01117054302.56
266 rdf:type schema:Person
267 sg:person.01132635714.61 schema:affiliation grid-institutes:grid.412484.f
268 schema:familyName Oh
269 schema:givenName Byung-Hee
270 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01132635714.61
271 rdf:type schema:Person
272 sg:person.01147373015.99 schema:affiliation grid-institutes:grid.412484.f
273 schema:familyName Lee
274 schema:givenName Hae-Young
275 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01147373015.99
276 rdf:type schema:Person
277 sg:person.01246601246.27 schema:affiliation grid-institutes:grid.412484.f
278 schema:familyName Kwon
279 schema:givenName Yoo-Wook
280 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01246601246.27
281 rdf:type schema:Person
282 sg:person.01250553160.10 schema:affiliation grid-institutes:grid.412484.f
283 schema:familyName Kim
284 schema:givenName Ju-Young
285 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01250553160.10
286 rdf:type schema:Person
287 sg:person.01254550333.69 schema:affiliation grid-institutes:grid.412484.f
288 schema:familyName Kang
289 schema:givenName Hyun-Jae
290 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01254550333.69
291 rdf:type schema:Person
292 sg:person.01300017742.41 schema:affiliation grid-institutes:grid.412484.f
293 schema:familyName Cho
294 schema:givenName Hyun-Jai
295 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01300017742.41
296 rdf:type schema:Person
297 sg:person.01357663360.74 schema:affiliation grid-institutes:grid.412484.f
298 schema:familyName Kim
299 schema:givenName Baek-Kyung
300 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01357663360.74
301 rdf:type schema:Person
302 sg:person.0661601052.43 schema:affiliation grid-institutes:grid.412484.f
303 schema:familyName Park
304 schema:givenName Young-Bae
305 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0661601052.43
306 rdf:type schema:Person
307 sg:person.0723732564.37 schema:affiliation grid-institutes:grid.412484.f
308 schema:familyName Lee
309 schema:givenName Joo-Eun
310 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0723732564.37
311 rdf:type schema:Person
312 sg:pub.10.1038/nm1175 schema:sameAs https://app.dimensions.ai/details/publication/pub.1045090677
313 https://doi.org/10.1038/nm1175
314 rdf:type schema:CreativeWork
315 grid-institutes:grid.31501.36 schema:alternateName Molecular Medicine and Biopharmaceutical Sciences, Seoul National University, Seoul, Korea
316 schema:name Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
317 Innovative Research Institute for Cell Therapy, Seoul National University Hospital, Seoul, Korea
318 Molecular Medicine and Biopharmaceutical Sciences, Seoul National University, Seoul, Korea
319 National Research Laboratory for Stem Cell Niche, Seoul National University College of Medicine, Seoul, Korea
320 rdf:type schema:Organization
321 grid-institutes:grid.412484.f schema:alternateName Innovative Research Institute for Cell Therapy, Seoul National University Hospital, Seoul, Korea
322 schema:name Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
323 Innovative Research Institute for Cell Therapy, Seoul National University Hospital, Seoul, Korea
324 National Research Laboratory for Stem Cell Niche, Seoul National University College of Medicine, Seoul, Korea
325 rdf:type schema:Organization
 




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


...