Vitamins C and E attenuate plasminogen activator inhibitor-1 (PAI-1) expression in a hypercholesterolemic porcine model of angioplasty

Background: The plasminogen activator inhibitor-1 (PAI-1), which modulates fibrinolysis and cell migration, may influence proteolysis and neointimal f ormation in the arterial wall contributing to restenosis after vascular inj ury. Antioxidants have been proposed as inhibiting multiple proatherogenic events. We explore the effect of vitamins C and E on PAI-1 expression in an experimental model of angioplasty in hypercholesterolemic pigs. Methods an d results: A total of 44 Yucatan minipigs were divided into three diet grou ps: a normal-cholesterol (NC), a high-cholesterol (HC), and a high-choleste rol plus vitamins C+E (HCV) group. Balloon injury was induced in the right internal iliac artery 4 weeks after initiation of either dietary regimen, a nd plasma and tissue samples were taken at different time periods to measur e PAI-1 activity and vascular inhibitor expression. The cholesterol-rich di et induced an increased in vascular PAI-1 expression in the intima, media a nd adventitia which was markedly reduced in the HCV group. After injury, se vere structural changes were observed in NC and HC animals associated with increased systemic PAT-1 activity (P<0.001) and local PAT-1 expression bein g more intense in HC group. Vitamins C and E significantly reduced plasma P AI-1 activity (P=0.018) and attenuated the inhibitor expression as compared with HC. Conclusions: This experimental study in a porcine model of hyperc holesterolemia demonstrates that vitamins C and E reduce local and systemic PAI-1 induced after angioplasty as well as the hyperchoresterolemia-induce d vascular PAT-1. (C) 2001 Elsevier Science B.V. All rights reserved.