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2004 Fiscal Year Final Research Report Summary

Regulation of smooth muscle cell function and arteriogenesis by glycated collagen and its receptor

Research Project

Project/Area Number 15590953
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Metabolomics
Research InstitutionOsaka City University

Principal Investigator

KOYAMA Hidenori  Osaka City Univ, Med, Lecturer, 大学院・医学研究科, 講師 (80301852)

Co-Investigator(Kenkyū-buntansha) YAMAMOTO Hiroshi  Kanazawa University, Professor, 大学院・医学系研究科, 教授 (00115198)
Project Period (FY) 2003 – 2004
KeywordsDiabetes mellitus / arteiogenesis / advanced glycation endproduct / receptor for AGE (RAGE) / smooth muscle cell / extracellular matrix / collagen type 1 / angiogenesis regulatory factors
Research Abstract

It has been shown that patients and experimental animal models with diabetes have a lesser ability to develop collateral blood vessels in arterial occlusion. However, the molecular and cellular mechanism underlying impaired arteriogenesis in diabetes is not known. In the present study, we examined the role of advanced glycation endproducts, AGE, and its receptor, RAGE, in diabetes-associated impaired smooth muscle cell (SMC) function and arteriogenesis. On glycolaldehyde-induced glycated form of type 1 fibrillar collagen (AGE-collagen), basal or PDGF-stimulated SMC migration was markedly decreased as compared with SMC cultured on native collagen. Analyses of candidate receptors for type 1 collagen revealed that expression of α2 integrins is suppressed, while levels of αv integrins are upregulated in SMC cultured on AGE-collagen. Culture on AGE collagen suppresses secretion and mRNA expression of vascular endothelial growth factor (VEGF), but enhances mRNA expression of thrombospondin-1, an inhibitor of angiogenesis. To examine arteriogenesis in vivo, we subcutaneously implanted VEGF-containing matrigel to streptozotocin-induced diabetic or control mice. In diabetic mice, numbers of α-actin positive SMC or pericytes migrated into matrigel was decreased by 25% as compared with control mice. Similarly CD31-positive endothelial cells infiltrated less in diabetic mice. Importantly, impaired migration of both SMC and endothelial cells into matrigel in diabetes was completely restored in RAGE-deficient mice. Thus, AGE-RAGE system appears to play fundamental role in impaired arteriogenesis in diabetes.

  • Research Products

    (12 results)

All 2005 2004

All Journal Article (12 results)

  • [Journal Article] Platelet in progression of atherosclerosis2005

    • Author(s)
      Koyama H, Nishizawa Y
    • Journal Title

      Current Diabetes Review 1(印刷中)

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Platelet in progression of atherosclerosis : a potential target in diabetic patients2005

    • Author(s)
      Koyama H, Nishizawa Y.
    • Journal Title

      Current Diabetes Review (in press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Roles of metabolic and endocrinological alterations in atherosclerosis and cardiovascular disease in renal failure2004

    • Author(s)
      Nishizawa Y, Shoji T, Emoto M, Koyama H, et al.
    • Journal Title

      Seminars in Nephrology 24(5)

      Pages: 423-425

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Statins inhibit in vitro calcification of human vascular smooth muscle cells induced by inflammatory mediator2004

    • Author(s)
      Kizu A, Shioi A, Jono S, Koyama H, et al.
    • Journal Title

      Journal of Cellular Biochemistry 93(5)

      Pages: 1011-1019

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Short-term aerobic exercise improves arterial stiffness in type 2 diabetes.2004

    • Author(s)
      Yokoyama H, Emoto M, Fujiwara S, Motoyama K, Morioka T, Koyama H, et al.
    • Journal Title

      Diabetes Research Clinical Practice 65(2)

      Pages: 85-93

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Effects of aerobic exercise on plasma adiponectin levels and insulin resistance in type 2 diabetes.2004

    • Author(s)
      Yokoyama H, Emoto M, Araki T, Fujiwara S, Motoyama K, Morioka T, Koyama H, et al.
    • Journal Title

      Diabetes Care 27(7)

      Pages: 1756-1758

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Arterial stiffness in predialysis patients with uremia.2004

    • Author(s)
      Shinohara K, Shoji T, Tsujimoto Y, Kimoto E, Tahara H, Koyama H, et al.
    • Journal Title

      Kidney International 65(3)

      Pages: 936-943

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Roles of metabolic and endocrinological alterations in atherosclerosis and cardiovascular disease in renal failure : another form of metabolic syndrome.2004

    • Author(s)
      Nishizawa Y, Shoji T, Emoto M, Koyama H, Tahara H, Fukumoto S, Inaba M, Ishimura E, Miki T
    • Journal Title

      Semin Nephrol 24

      Pages: 423-425

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Statins inhibit in vitro calcification of human vascular smooth muscle cells induced by inflammatory mediators.2004

    • Author(s)
      Kizu A, Shioi A, Jono S, Koyama H, Okuno Y, Nishizawa Y
    • Journal Title

      Journal of Cellular Biochemistry 93

      Pages: 1011-1019

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Short-term aerobic exercise improves arterial stiffness in type 2 diabetes.2004

    • Author(s)
      Yokoyama H, Emoto M, Fujiwara S, Motoyama K, Morioka T, Koyama H, Shoji T, Inaba M, Nishizawa Y
    • Journal Title

      Diabetes Research and Clinical Practice 65

      Pages: 85-93

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Effect of aerobic exercise on plasma adiponectin levels and insulin resistance in type 2 diabetes.2004

    • Author(s)
      Yokoyama H, Emoto M, Araki T, Fujiwara S, Motoyama K, Morioka T, Koyama H, Shoji T, Okuno Y, Nishizawa Y
    • Journal Title

      Diabetes Care 27

      Pages: 1756-1758

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Arterial stiffness in predialysis patients with uremia.2004

    • Author(s)
      Shinohara K, Shoji T, Tsujimoto Y, Kimoto E, Tahara H, Koyama H, Emoto M, Ishimura E, Miki T, Tabata T, Nishizawa Y
    • Journal Title

      Kidney International 65

      Pages: 936-943

    • Description
      「研究成果報告書概要(欧文)」より

URL: 

Published: 2007-12-13  

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