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2002 Fiscal Year Final Research Report Summary

Regulation of smooth muscle cell function by glycated polymerized type 1 collagen

Research Project

Project/Area Number 13671197
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)

Project Period (FY) 2001 – 2002
Keywordsatherosclerosis / diabetes / extracelluar matrix / AGE / integrin / angiogenesis / collagen type I / matrix metalloproteinase
Research Abstract

Patients and experimental animal models with diabetes have a lesser ability to develop collateral blood vessels in arterial occlusion. However, the mechanism underlying impaired arteriogenesis in diabetes is unclear. In this study, we examined the effects of glycated polymerized type 1 collagen fibrils (AGE-collagen) on functions of vascular smooth muscle cells (SMC). Random or PDGF-directed SMC migration was markedly suppressed on AGE-collagen as compared with native collagen. Analyses of integrin expression by Northern or Western blot analysis on AGE-collagen revealed that the levels of α2 integrin was markedly suppressed as compared with native collagen. In contrast, αv integrin was significantly upregulated on AGE-collagen. The effects on SMC migration on AGE-collagen of blocking antibodies against candidate receptors for AGE-collagen revealed that not αv integrins blockade but CD36 inhibition restored SMC migration inhibited on AGE-collagen. Moreover, expression of vascular endothelial growth factor and matrix metalloproteinase-2, pro-angiogenic factors, was suppressed on AGE-collagen, while thrombospondin-1, an anti-angiogenic factor, was upregulated. Thus, impaired SMC migration and dynamic altered expression of angiogenesis regulators by AGE-collagen may contribute to decreased formation of collateral blood vessels in diabetes.

  • Research Products

    (27 results)

All Other

All Publications (27 results)

  • [Publications] Morioka T, Koyama H, et al.: "Role of H1-calponin in pancreatic AR42J cell differentiation into insulin-producing cells"Diabetes. 52(3). 760-766 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kimoto E, Shoji T, Shinohara K, Inaba M, Okuno Y, Miki T, Koyama H et al.: "Preferential stiffening of central over peripheral arteries in type 2 diabetes"Diabetes. 52(2). 2230-2237 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shoji T, Fukumoto M, Kimoto E, Shinohara K, Emoto M, Tahara H, Koyama H et al.: "Antibody to oxidized low-density lipoprotein and cardiovascular mortality in end-stage renal disease"Kidney International. 62(6). 2230-2237 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Wada Y, Sugiyama A, Yamamoto T, Naito M, Noguchi N, et al.: "Lipid accumulation in smooth muscle cells under LDL loading is independent of LDL receptor pathway and enhanced by hypoxic conditions"Arteriosclerosis, Thrombosis and Vascular Biology. 22(10). 1721-1719 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tanaka S, Koyama H, et al.: "Fibrillar collagen regulation of plasminogen activator inhibitor-1 is involved in altered smooth muscle cell migration"Arteriosclerosis, Thrombosis and Vascular Biology. 22(10). 1573-1578 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ichii T, Koyama H et al.: "Thrombospondin-1 mediates smooth muscle cell proliferation induced by interaction with human platelets"Arteriosclerosis, Thrombosis and Vascular Biology. 22(8). 1286-1292 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shioi A, Katagi M, Okuno Y, Mori K, Jono S, Koyama H, Nishizawa: "Induction of bone-type alkaline phosphatase in human vascular smooth muscle cells : roles of tumor necrosis factor-α and oncostatin M derived from macrophage"Circulation Research. 91(1). 9-16 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shinohara K, Shoji T, Emoto M, Tahara H, Koyama H et al.: "Insulin resistance as an independent predictor of cardiovascular mortality in patients with end-stage renal disease"Journal of American Society of Nephrology. 13(7). 1894-1900 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Maeno T, Koyama H et al.: "The 807T allele in alpha2 integrin is protective against atherosclerotic arterial wall thickening and the occurrence of plaque in patients with type 2 diabetes"Diabetes. 51(5). 1523-1528 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Motamed K, Funk SE, Koyama H et al.: "Inhibition of PDGF-stimulated and matrix-mediated proliferation of human vascular smooth muscle cells by SPARS is independent of changes in cell shape or cyclin-dependent kinase inhibitors"Journal of Cellular Biochemistry. 84(4). 759-771 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 横出正之, 福尾恵介, 吉栖正生, 小山英則: "座談会:加齢と血管病学をどのように考えるか"分子心血管病. 3(5). 521-532 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 福井 淳, 小山英則: "動脈石灰化の分子機構"分子心血管病. 3(5). 565-570 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 小山英則: "細胞分化・増殖における接着因子の役割"CLINICAL CALCIUM. 12(5). 587-593 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 福本真也, 小山英則, 西沢良記: "動脈硬化症の進展と血管平滑筋細胞"臨床透析. 18(1). 19-28 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 小山英則, 福本真也, 西沢良記: "細胞外マトリックスと血管リモデリング"現代医療. 33(12). 3021-3028 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nishizawa Y, Koyama H: "CALCIUM IN INTERNAL MEDICINE"Springer (Morii H, Nishizawa Y, Massry SG eds). 504 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Morioka T, Koyama H, Yamamura H, Tanaka S, Fukumoto S, Emoto M, Mizuguchi H, Hayakawa T, Kojima I, Takahashi K, Nishizawa Y.: "Role of H1-calponin in pancreatic AR42J cell differentiation into insulin-producing cells."Diabetes. 52(3). 760-766 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kimoto E, Shoji T, Shinohara K, Inaba M, Okuno Y, Miki T, Koyama H. Emoto M, Nishizawa Y.: "Preferential stiffening of central over peripheral arteries in type 2 diabetes."Diabetes. 52(2). 448-452 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shoji T, Fukumoto M, Kimoto E, Shinohara K, Emoto M, Tahara H, Koyama H, Ishimura E, Nakatani T, Miki T, Tsujimoto Y, Tabata T, Nishizawa Y.: "Antibody to oxidized low-density lipoprotein and cardiovascular mortality in end-stage renal disease."Kidney Internatinal. 62(6). 2230-2237 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Wada Y, Sugiyama A, Yamamoto T, Naito M, Noguchi N, Yokoyama S, Tsujita M, Kawabe Y, Kobayashi M, Izumi A, Kohro T, Tanaka T, Taniguchi H, Koyama H, Hirano K, Yamashita S, Matsuzawa Y, Niki E, Hamakubo T, Kodama T.: "Lipid accumulation in smooth muscle cells under LDL loading is independent of LDL receptor pathway and enhanced by hypoxic conditions."Arteriosclerosis Thrombosis and Vascular Biology. 22(10). 1712-1719 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tanaka S, Koyama H, Ichii T, Shioi A, Hosoi M, Raines EW, Nishizawa Y.: "Fibrillar collagen regulation of plasminogen activator inhibitor-1 is involved in altered smooth muscle cell migration."Arteriosclerosis Thrombosis and Vascular Biology. 22(10). 1573-1578 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ichii T, Koyama H, Tanaka S, Shioi A, Okuno Y, Otani S, Nishizawa Y.: "Thrombospondin-1 mediates smooth muscle cell proliferation induced by interaction with human platelets."Arteriosclerosis Thrombosis and Vascular Biology. 22(8). 1286-1292 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shioi A, Katagi M, Okuno Y, Mori K, Jono S, Koyama H, Nishizawa Y.: "Induction of bone-type alkaline phosphatase in human vascular smooth muscle cells: roles of tumor necrosis factor-alpha and oncostatin M derived from macrophages."Circulation Research. 12;91(1). 9-16 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shinohara K, Shoji T, Emoto M, Tahara H, Koyama H, Ishimura E, Miki T, Tabata T, Nishizawa Y.: "Insulin resistance as an independent predictor of cardiovascular mortality in patients with end-stage renal disease."Journal of American Society of Nephrology. 13(7). 1894-1900 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Maeno T, Koyama H, Tahara H, Komatsu M, Emoto M, Shoji T, Inaba M, Miki T, Okuno Y, Nishizawa Y.: "The 807T allele in alpha2 integrin is protective against atherosclerotic arterial wall thickening and the occurrence of plaque in patients with type 2 diabetes."Diabetes. 51(5). 1523-1528 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Motamed K, Funk SE, Koyama H, Ross R, Raines EW, Sage EH.: "Inhibition of PDGF-stimulated and matrix-mediated proliferation of human vascular smooth muscle cells by SPARC is independent of changes in cell shape or cyclin-dependent kinase inhibitors."Journal of Cellular Biochemistry. 84(4). 759-771 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nishizawa Y and Koyama H.: "Atherosclerosis., CALCIUM IN INTERNAL MEDICINE. Morii H, Nishizawa Y and Massry SG eds."Springer, London. 447-460 (2002)

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

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Published: 2004-04-14  

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