Systemic tissue inhibitor of metalloproteinase-1 gene delivery reduces neointimal hyperplasia in balloon-injured rat carotid artery

Metalloproteinases (MMP)-2 and MMP-9 play a role in smooth muscle cell (SMC) migration from the media to the intima following arterial injury. Intravenous administration of adenovirus encoding tissue inhibitor of metalloproteinase-1 (TIMP-1) into balloon-injured rat arteries (3 X 10(11) viral particles/rat; n = 7) resulted in a transient expression of TIMP-1 and a significant inhibition of neointima thickening within 16 days (similar to40% vs. control; P = 0.012). Three days after injury, the number of intimal SMCs was decreased by similar to98% in TIMP-l-treated rats. However, no alteration was seen in intimal SMC proliferation after 13 days of injury. Therefore, our results show that systemic gene transfer of TIMP-1 is a promising approach in early restenosis treatment. (C) 2002 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.