Neointima formation and thrombosis after vascular injury in transgenic mice overexpressing plasminogen activator inhibitor-1 (PAI-1).
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| Abstract |
The controversial role of plasminogen activator inhibitor-1 (PAI-1) in neointima formation and restenosis was studied with the use of a vascular injury model in transgenic mice overexpressing murine PAI-1 (PAI-1 Tg) and in wild-type (WT) controls. Despite the high circulating PAI-1 levels in the PAI-1 Tg mice (52 +/- 9.8 ng mL-1 vs. 0.76 +/- 0.17 ng mL-1 in WT mice), no significant fibrin deposition was observed in non-injured femoral arteries of 8- to 12-week-old mice. Two weeks after severe electric injury, extensive and comparable fibrin deposition was observed in both genotypes, despite a significantly reduced in situ fibrinolytic activity in arterial sections of the PAI-1 Tg mice. The neointimal and medial areas were similar in WT and PAI-1 Tg mice, resulting in comparable intima/media ratios (e.g. 0.94 +/- 0.25 and 1.04 +/- 0.17 at the center of the injury). Nuclear cell counts in cross-sectional areas of the neointima of the injured region were also comparable in arteries from WT and PAI-1 Tg mice (224 +/- 63, 233 +/- 20), and the distribution pattern of alpha-actin-positive smooth muscle cells was similar. These findings indicate that in a vascular injury model that induces extensive and persistent fibrin deposition in femoral arteries of mice, overexpression of PAI-1 does not affect neointima formation.
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| Authors | H R Lijnen, B Van Hoef, K Umans, D Collen |
| Journal | Journal of thrombosis and haemostasis : JTH (J Thromb Haemost) Vol. 2 Issue 1 Pg. 16-22 (Jan 2004) ISSN: 1538-7933 [Print] England |
| PMID | 14717961 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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