Altered balance between extracellular proteolysis and antiproteolysis is associated with adaptive coronary arteriogenesis

Wei jun Cai, Regina Vosschulte, Abdollah Afsah-Hedjri, Sophie Koltai, Elisabeth Kocsis, Dimitri Scholz, Sawa Kostin, Wolfgang Schaper, Jutta Schaper

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74 Citations (Scopus)


To study the role of extracellular proteolysis and antiproteolysis during adaptive arteriogenesis (collateral vessel growth) we took 58 collaterals at various developmental stages from 14 dogs with chronic occlusion of the left circumflex coronary artery (LCx) by ameroid constrictor. Immunofluorence and quantitative immunofluorescence with antibodies against α-smooth muscle actin, desmin, matrix metalloproteinases 2 (MMP-2), MMP-9. tissue inhibitor of metalloproteinases 1 (TIMP-1) and 2 (TIMP-2). urokinase-type plasminogen activator (u-PA) and its inhibitor-1 (PAI-1) were studied with confocal microscopy. Additionally, SDS-PAGE zymography was employed, We found that in normal coronary arteries. MMP-2. MMP-9 and PAI-1 were present in all layers of the wall in small amounts. TIMP-1 was found only in smooth muscle cells. In contrast, in growing collaterals, MMP-2 and MMP-9 were 3.4-fold and 4.1-fold higher in the neointima than in the media respectively. TIMP-1 was 4.4-fold higher in the media over the growing neointima. Zymography showed MMP-2 and MMP-9 activated. PAI-1 was increased, especially in the growing neointima where it was 1.4-fold higher. In mature collaterals. MMP-2 and MMP-9 were downregulated in the neointima, 1.4-fold and 1.3-fold higher over the media. TIMP-1 was 1.4-fold increased in the neointima but PAI-1 was downregulated. Desmin and α-smooth muscle actin were significantly increased in the neointima compared to growing vessels. U-PA was moderately increased in growing vessels. TIMP-2 was not detectable in collaterals. We conclude that expression of MMP-2 and 9. TIMP-1 and PAI-1 showed a spatial and temporal pattern which is closely associated with the development of collateral vessels. The shift of the balance between proteolysis and antiproteolysis is regulated not only by MMPs and TIMP-1, but also by the PA-PAI system. (C) 2000 Academic Press.

Original languageEnglish
Pages (from-to)997-1011
Number of pages15
JournalJournal of Molecular and Cellular Cardiology
Issue number6
Publication statusPublished - Jan 1 2000


  • Arteriogenesis
  • Collateral vessel growth
  • Dog
  • Extracellular matrix
  • Metalloproteinases
  • Vascular remodeling

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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