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Am J Physiol Heart Circ Physiol 284: H23-H30, 2003. First published September 5, 2002; doi:10.1152/ajpheart.00240.2002
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Vol. 284, Issue 1, H23-H30, January 2003

Role of MMPs and plasminogen activators in angiogenesis after transmyocardial laser revascularization in dogs

Wei Li, Kuniyoshi Tanaka, Yukio Chiba, Tetsuya Kimura, Kouichi Morioka, Takahiko Uesaka, Akio Ihaya, Masato Sasaki, Takeshi Tsuda, and Narihisa Yamada

Second Department of Surgery, Fukui Medical University, Fukui 9101193, Japan

We examined the role of matrix metalloproteinases (MMPs), tissue inhibitors of MMP (TIMPs), and plasminogen activator (PA) in transmyocardial laser revascularization (TMLR)-induced angiogenesis. TMLR was accomplished with a carbon dioxide laser in seven dogs whose left anterior descending coronary artery (LAD) was ligated. Seven control dogs underwent only LAD ligation, and four dogs underwent a sham operation, consisting only of a left thoracotomy. Two weeks later, transmural myocardial samples were harvested from the distributions of the LAD and the left circumflex artery for substrate zymography, immunohistochemical staining, and in situ zymography. MMP-1, MMP-2, TIMP-1, TIMP-2, and urokinase-type PA levels in the distribution of the LAD were higher in the laser group than in the control or sham group. Counts of von Willebrand factor-positive microvessels and smooth muscle alpha -actin-positive arterioles demonstrated that the angiogenesis and ateriogenesis was promoted in the laser group and correlated directly with the number of MMP-stained microvessels. We conclude that TMLR induces the expression of MMPs, TIMPs, and urokinase-type PA and that these proteinases play an important role in angiogenesis after TMLR.

matrix metalloproteinase


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