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-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.
Lijnen
H R
HR
Center for Molecular and Vascular Biology, University of Leuven, Belgium. roger.lijnen@med.kuleuven.ac.be
Van Hoef
B
B
Umans
K
K
Collen
D
D
D000818:Animals; D003251:Constriction, Pathologic; D023903:Coronary Restenosis / Q000209:etiology; D005260:Female; D005263:Femoral Artery / Q000293:injuries* / Q000473:pathology / Q000503:physiopathology*; D005342:Fibrinolysis; D015870:Gene Expression; D006083:Graft Occlusion, Vascular / Q000209:etiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009389:Neovascularization, Pathologic; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000502:physiology*; D013927:Thrombosis / Q000209:etiology / Q000473:pathology / Q000503:physiopathology
D017395:Plasminogen Activator Inhibitor 1