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Am J Physiol Heart Circ Physiol (September 5, 2002). doi:10.1152/ajpheart.00240.2002
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Articles in PresS, published online ahead of print September 5, 2002
Am J Physiol Heart Circ Physiol, 10.1152/ajpheart.00240.2002
Submitted on March 20, 2002
Accepted on August 26, 2002

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

Li Wei1, Tanaka Kuniyoshi1*, Chiba Yukio1, Kimura Tetsuya1, Morioka Kouichi1, Uesaka Takahiko1, Ihaya Akio1, Sasaki Masato1, Tsuda Takeshi1, and Yamada Narihisa1

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

* To whom correspondence should be addressed. E-mail: Kunitan{at}fmsrsa.fukui-med.ac.jp.

We examined the role of matrix metalloproteinase (MMP), tissue inhibitor of MMP (TIMP), and plasminogen activator in transmyocardial laser revascularization (TMLR) induced angiogenesis. TMLR was accomplished with a carbon dioxide laser in 7 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, -2, TIMP-1, -2 and urokinase-type plasminogen activator (u-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 {alpha} smooth muscle actin-positive arteriolae 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 uPA, and that these proteinases play an important role in angiogenesis after TMLR.




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