血管平滑筋細胞に対するフィブリノゲン,フィブリンおよびそれらの分解産物の影響 Effects of fibrinogen, fibrin and their degradation products on the behaviour of vascular smooth muscle cells

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著者

    • 内藤 通孝 NAITO Michitaka
    • 名古屋大学大学院医学研究科発育・加齢医学講座(老年科学) Department of Geriatrics, Nagoya University Graduate School of Medicine

抄録

The transition of fibrinogen to fibrin and to their degradation products within the arterial wall has been reported to be accompanied by atherosclerotic progression. A major step in the pathogenesis of atherosclerosis is the vectorial migration of vascular smooth muscle cells (SMCs) from the arterial media through the internal elastic lamina into the intima and their subsequent proliferation in the intima. I have been studying the effects of fibrinogen, fibrin and their degradation products on the behaviour, particularly migration, of SMCs.<br>Fibrinogen/fibrin stimulates the adhesion and migration of SMCs and their effects are mediated by both the RGD-containing region of the α chain of fibrinogen/fibrin and integrin αvβ3 on the cell surface. SMCs migrate into fibrin gel even with no other chemotactic stimuli. SMCs displayed two-fold increase in migration into crosslinked fibrin gels compared to non-crosslinnked gels, suggesting the importance of fibrin crosslinking by factor XIIIa on its three-dimensional structure for the migration of SMCs. Fibrin gels prepared with batroxobin, which cleaves only fibrinopeptide A, with ACTS, which cleaves only fibrinopeptide B, and with protamine sulfate, which cleaves nothing, but forms a fibrin-like gel, induce migration of SMCs in a manner similar to the gel prepared with thrombin, suggesting that the cleavage of fibrinopeptides is not involved in the migration of SMCs. Both anti-fibrinogen fragment D and E antibodies inhibit the migration of SMCs into fibrin gel, suggesting that both D and E regions of fibrin are involved in the migration of SMCs into fibrin gel. The migration of SMCs into fibrin gel also depends on the RGD-containing region and integrin αvβ3. Both fibrinogen fragments D and E inhibit the migration of SMCs into fibrin gels, suggesting that these fragments may be involved in the regulation of SMC migration into fibrin gel as the result of fibrinolysis.<br>Although subcultured SMCs usually show a synthetic phenotype, the behaviour of contractile SMCs may be crucial for the subsequent migration of the cells. We employed an in vitro assay system to evaluate the effects of fibrin gels on the migration of SMCs from explants taken from rabbit aorta. αvβ3 integrin and the RGD-containing region are involved in the migration of SMCs into the fibrin gels. SMCs which migrated from the explants showed positive staining with monoclonal antibodies against SMC myosin heavy chain isoforms, SMemb, SM1 and SM2, suggesting that they are in an intermediate state changing from a contractile to synthetic state.<br>These findings show that fibrin (ogen) itself induces adhesion and migration of SMCs without other chemotactic or chemokinetic substances, suggesting a crucial role for fibrin (ogen) in the development and progression of such vascular diseases as atherosclerosis, thrombosis and restenosis following balloon angioplasty.

収録刊行物

  • 日本老年医学会雑誌

    日本老年医学会雑誌 37(6), 458-463, 2000-06-25

    The Japan Geriatrics Society

参考文献:  27件中 1-27件 を表示

被引用文献:  1件中 1-1件 を表示

  • 食と動脈硬化

    内藤 通孝

    日本食生活学会誌 = Journal for the integrated study of dietary habits 19(4), 307-319, 2009-03-30

    参考文献80件

各種コード

  • NII論文ID(NAID)
    10008487676
  • NII書誌ID(NCID)
    AN00199010
  • 本文言語コード
    JPN
  • 資料種別
    REV
  • ISSN
    03009173
  • NDL 記事登録ID
    5439692
  • NDL 雑誌分類
    ZS21(科学技術--医学--内科学)
  • NDL 請求記号
    Z19-25
  • データ提供元
    CJP書誌  CJP引用  NDL  J-STAGE 
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