Overexpression of matrix metalloproteinase-9 promotes intravascular thrombus formation in porcine coronary arteries in vivo

Kunio Morishige, Hiroaki Shimokawa, Yasuharu Matsumoto, Yasuhiro Eto, Toyokazu Uwatoku, Kotaro Abe, Katsuo Sueishi, Akira Takeshita

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Objective: Matrix metalloproteinases (MMPs) cause extracellular matrix degradation and may be involved in the rupture of atherosclerotic plaques by degrading fibrous cap, resulting in the intravascular thrombus formation. Here we examined whether local overexpression of MMP-9 alters the characteristics of arteriosclerotic vascular lesions and promotes thrombosis after balloon injury in porcine coronary arteries in vivo. Methods and results: Balloon angioplasty was performed in the left coronary arteries followed by injection of adenovirus vector solution encoding either MMP-9 or β-galactosidase (β-gal) gene into the injured coronary arteries. Three weeks after the gene transfer, histological examination demonstrated that macroscopic intravascular thrombus formation was noted at the MMP-9-transfected site but not at the β-gal-transfected site. Microscopic intramural thrombus area was significantly larger at the MMP-9-transfected site as compared to the β-gal-transfected site. Co-transfection of tissue inhibitor of metalloproteinase-1 (TIMP-1) with MMP-9 prevented the intravascular thrombus formation in vivo. Western blot analysis revealed the reduced expression of intact tissue factor pathway inhibitor-1 and the increased tissue factor (TF) expression at the MMP-9-transfected sites. Conclusion: These results provide the first in vivo evidence that overexpression of MMP-9 promotes intravascular thrombus formation after balloon injury due in part to the activation of TF-mediated coagulation cascade.

Original languageEnglish
Pages (from-to)572-585
Number of pages14
JournalCardiovascular research
Volume57
Issue number2
DOIs
Publication statusPublished - Feb 1 2003

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Matrix Metalloproteinase 9
Coronary Vessels
Thrombosis
Swine
Thromboplastin
Galactosidases
Tissue Inhibitor of Metalloproteinase-1
Balloon Angioplasty
Wounds and Injuries
Atherosclerotic Plaques
Matrix Metalloproteinases
Adenoviridae
Genes
Extracellular Matrix
Transfection
Blood Vessels
Rupture
Western Blotting
Injections

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Overexpression of matrix metalloproteinase-9 promotes intravascular thrombus formation in porcine coronary arteries in vivo. / Morishige, Kunio; Shimokawa, Hiroaki; Matsumoto, Yasuharu; Eto, Yasuhiro; Uwatoku, Toyokazu; Abe, Kotaro; Sueishi, Katsuo; Takeshita, Akira.

In: Cardiovascular research, Vol. 57, No. 2, 01.02.2003, p. 572-585.

Research output: Contribution to journalArticle

Morishige, Kunio ; Shimokawa, Hiroaki ; Matsumoto, Yasuharu ; Eto, Yasuhiro ; Uwatoku, Toyokazu ; Abe, Kotaro ; Sueishi, Katsuo ; Takeshita, Akira. / Overexpression of matrix metalloproteinase-9 promotes intravascular thrombus formation in porcine coronary arteries in vivo. In: Cardiovascular research. 2003 ; Vol. 57, No. 2. pp. 572-585.
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