Inhibitory role of plasminogen activator inhibitor-1 in arterial wound healing and Neointima formation: A gene targeting and gene transfer study in mice

• Published in: Circulation (New York, N.Y.) N.Y.), 1997-11, Vol.96 (9), p.3180-3191
• Main Authors: CARMELIET, P, MOONS, L, LIJNEN, R, JANSSENS, S, LUPU, F, COLLEN, D, GERARD, R. D
• Format: Article
• Language: English
• Subjects: Adenoviridae - genetics; Animals; Biological and medical sciences; Cell Division; Cell Movement; Diseases of the cardiovascular system; Endothelium, Vascular - cytology; Endothelium, Vascular - physiology; Female; Gene Targeting; Gene Transfer Techniques; Male; Medical sciences; Mice; Mice, Inbred C57BL; Muscle, Smooth, Vascular - pathology; Plasminogen Activator Inhibitor 1 - analysis; Plasminogen Activator Inhibitor 1 - genetics; Plasminogen Activator Inhibitor 1 - physiology; Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects); Thrombosis - prevention & control; Vascular Diseases - prevention & control; Wound Healing
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/01.CIR.96.9.3180

Plasminogen-deficient mice display impaired vascular wound healing and reduced arterial neointima formation after arterial injury, suggesting that inhibition of plasmin generation might reduce arterial neointima formation. Therefore, we studied the consequences of plasminogen activator inhibitor-1 (PAI-1) gene inactivation and adenoviral PAI-1 gene transfer on arterial neointima formation. Neointima formation was evaluated in PAI-1-deficient (PAI-1(-/-)) mice with perivascular electric or transluminal mechanical injury. PAI-1 deficiency improved vascular wound healing in both models: the cross-sectional neointimal area was 0.001+/-0.001 mm2 in PAI-1(+/+) and 0.016+/-0.008 mm2 in PAI-1(-/-) mice within 1 week after electric injury (P