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Role of lipoprotein-associated lysophospholipids in cellular activities of vascular smooth muscle cells

Research Project

Project/Area Number 17590914
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Metabolomics
Research InstitutionGunma University

Principal Investigator

TOMURA Hideaki  Gunma University, Institute for Molecular and Cellular Regulation, Associate Professor, 生体調節研究所, 助教授 (70217553)

Co-Investigator(Kenkyū-buntansha) OKAJIMA Fumikazu  Gunma University, Institute for Molecular and Cellular Regulation, Professor, 生体調節研究所, 教授 (30142748)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
KeywordsLDL / HDL / Lysophosphatidic acid / Sphingosine 1-phosphate / vascular smooth muscle cells / LPA1 / S1P2 / LPA receptor antagonist / スフィンゴシン1リン酸 / 平滑筋細胞遊走 / 平滑筋細胞増殖
Research Abstract

Low-density lipoprotein (LDL) and provides cholesterol to cells, while high-density lipoprotein (HDL) removes excess cholesterol from artery walls. On the other hand, which molecule in the lipoprotein plays the role is not understood still well, although actions other than the cholesterol metabolism are known to the lipoprotein. Lipoproteins carry a variety of bioactive substances. We showed sphingosine 1-phosphate (S1P) and lysophosphatidic acid (LPA) were present in the lipoproteins. We also showed that LPA stimulates migratory response and S1P inhibits the response of vascular smooth muscle cells (VSMCs). These actions mimicked the LDL and HDL actions. Since migration of VSMCs is a hallmark of the pathogenesis of atherosclerosis, we set up the hypothesis that LPA in the lipoprotein took part in the atherosclerosis promotion and S1P in the lipoprotein in the anti-atherosclerosis action. In fact, the LDL-induced migration of coronary artery smooth muscle cells (CASMCs) was markedly inhibited by the suppression of LPA1 receptor-activity. On the contrary, HDL-induced inhibition of LPA- and PDGF-induced migration was suppressed by the S1P2-receptor-activity. We measured the amount of S1P in LDL and HDL. The content of S1P is about 4-fold higher in HDL than in LDL, which supports the hypothesis. In addition, degradation of LPA component of LDL or antagonism of LPA receptors allowed LDL to inhibit the PDGF-induced migration. The inhibitory effect of LDL was suppressed by the inhibition of S1P2-receptor-activity. In conclusion, LPA/LPA1 receptors and S1P/S1P2 receptors mediate stimulatory and inhibitory migration response to LDL and HDL, respectively. A balance of not only the content of LPA and S1P in lipoproteins but also the signaling activity between LPA1 and S1P2 receptors may be crucial to determine whether the lipoprotein is a positive or negative regulator of CASMC migration.

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (22 results)

All 2007 2006 2005

All Journal Article (22 results)

  • [Journal Article] Role of lipoprotein-associated lysophospholipids in migratory activity of coronary artery smooth muscle cells2007

    • Author(s)
      Damirin, A., et al.
    • Journal Title

      Am J Physiol Heart Circ Physiol (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] HSF1 and constitutively active HSF1 improve vascular endothelial function (heat shock proteins improve vascular endothelial function)2007

    • Author(s)
      Uchiyama, T., et al.
    • Journal Title

      Atherosclerosis 190

      Pages: 321-329

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Cloning and expression of vacuolar proton-pumping ATPase subunits in the follicular epithelium of the bullfrog endolymphatic sac2007

    • Author(s)
      Yajima, S., et al.
    • Journal Title

      Zoolog Sci. 24

      Pages: 147-157

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Cloning and expression of vacuolar proton-pumping ATPase subunits in the follicular epithelium of bullfrog endolymphatic sac2007

    • Author(s)
      Yajima, S., et al.
    • Journal Title

      Zoolog Sci. 24

      Pages: 147-157

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Role of lipoprotein-associated lysophospholipids in migratory activity of coronary artery smooth muscle cells2007

    • Author(s)
      Damirin, A., et al.
    • Journal Title

      Am J Physiol Heart Circ Physiol. (In press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Simvastatin induces heat shock factor 1in vascular endothelial cells2006

    • Author(s)
      Uchiyama, T., et al.
    • Journal Title

      Atherosclerosis 188

      Pages: 265-273

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Role of scavenger receptor class B type I and sphingosine 1-phosphate receptors in high density lipoprotein-induced inhibition of adhesion molecule expression in endothelial cells2006

    • Author(s)
      Kimura, T., et al.
    • Journal Title

      J Biol Chem. 281

      Pages: 37457-37467

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Sphingosine 1-phosphate receptors mediate stimulatory and inhibitory signalings for expression of adhesion molecules in endothelial cells2006

    • Author(s)
      Kimura, T., et al.
    • Journal Title

      Cell Signal. 18

      Pages: 841-850

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Simvastatin induces heat shock factor 1 in vascular endothelial cells2006

    • Author(s)
      Uchiyama, T., et al.
    • Journal Title

      Atherosclerosis 188

      Pages: 265-273

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Role of scavenger receptor class B type I and sphingosine 1-phosphate receptors in high density lipoprotein-induced inhibition of adhesion molecule expression in endothelial cells2006

    • Author(s)
      Kimura, T., et al.
    • Journal Title

      J Biol Chem 281

      Pages: 37457-37467

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Simvastatin induces heat shock factor 1 in vascular exndothelial cells2006

    • Author(s)
      Uchiyama, T., et al.
    • Journal Title

      Atherosclerosis 188

      Pages: 265-73

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Role of scavenger receptor class B type 1 and sphingosine 1-phosphate receptors in high density lipoprotein-induced inhibition of adhesion molecule expression in endothelial cells2006

    • Author(s)
      Kimura, T., et al.
    • Journal Title

      J Biol Chem. 281

      Pages: 37457-67

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Prostaglandin I2 production and cAMP accumulation in response to acidic extracellular pH through OGR1 in human aortic smooth muscle cells2005

    • Author(s)
      Tomura, H., et al.
    • Journal Title

      J.Biol.Chem. 280

      Pages: 34458-34464

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Sphingosine 1-phosphate receptors mediate the lipid-induced cAMP accumulation through cyclooxygenase-2/prostaglandin I2 pathway in human coronary artery smooth muscle cells2005

    • Author(s)
      Damirin, A., et al.
    • Journal Title

      Mol.Pharmacol. 67

      Pages: 1177-1185

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Sphingosylphosphorylcholine antagonizes proton-sensing OCR1-mediated inositol phosphate production and cAMP accumulation2005

    • Author(s)
      Mogi, C., et al.
    • Journal Title

      J.Pharmaco.Sci. 99

      Pages: 160-167

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Proton-sensing and lysolipid-sensitive G-protein-coupled receptors : A novel role of multi-functional receptors2005

    • Author(s)
      Tomura, H., et al.
    • Journal Title

      Cell Signal. 17

      Pages: 1466-1476

    • Related Report
      2005 Annual Research Report
  • [Journal Article] High-density lipoprotein inhibits migration of vascular smooth muscle cells through its sphingosine 1-phosphate component2005

    • Author(s)
      Tamama, k., et al.
    • Journal Title

      Atherosclecosis 178

      Pages: 19-23

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Role of p38 mitogen-activated kinase and c-Jun terminalkinase in migration response to lysophosphatidic acid and sphingosine 1-phosphate in glioma cells2005

    • Author(s)
      Malchinkhuu, E., et al.
    • Journal Title

      Oncogene 24

      Pages: 6676-6688

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Sphingosine 1-phosphate inhibits migration and RANTES production in human bronchial smooth muscle cells2005

    • Author(s)
      Kawata, T., et al.
    • Journal Title

      Biochem.Biophys.Res.Commun. 331

      Pages: 640-647

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Study on action mode of sphingosine 1-phosphate in rat hepatocytes2005

    • Author(s)
      Im, YJ, et al.
    • Journal Title

      J.Pharmacol.Sci. 97

      Pages: 443-446

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Correlation of high density lipoprotein(HDL)-associated sphingosine 1-phosphate with serum levels of HDL-cholesterol and apolipoproteins2005

    • Author(s)
      Zhang, B., et al.
    • Journal Title

      Atherosclerosis. 178

      Pages: 199-205

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Identification of autotoxin as a neurite retration-inducing factor of PC12 cells in cerebrospinal fluid and its possible sources2005

    • Author(s)
      Sato, K., et al.
    • Journal Title

      J.Neurochem. 92

      Pages: 904-914

    • Related Report
      2005 Annual Research Report

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Published: 2005-04-01   Modified: 2016-04-21  

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