Neointima formation and thrombosis after vascular injury in transgenic mice overexpressing plasminogen activator inhibitor‐1 (PAI‐1)

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−1vs. 0.76 ± 0.17 ng mL−1in 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 situfibrinolytic 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 α‐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.