Role of Lysyl Oxidases in Neointima Development in Vascular Allografts

Background: Extracellular matrix deposition is the main factor inducing stenotic lesions in arterial grafts. Lysyl oxidases (LOX) play a key role in stabilizing collagen and elastin. Objective: To examine the repair response to arterial allografts in terms of LOX expression and collagen/elastin deposition using LOX inhibitors. Methods: Lewis/Fisher-344 rats were used as donors/recipients. Donor segments were grafted to the right iliac artery of recipients and retrieved 14/30 (short-term) or 90/180 days (long-term) after surgery. One group of animals was injected with a potent irreversible LOX inhibitor daily for 30 days. Results: Intimal hyperplasia increased in thickness until 90/180 days postsurgery. Elastin showed great expression in the neointima at 14/30 days and in the media at 90/180 days. LOX/LOXL1 were similarly expressed in the arterial wall during the first month. In the long term, their overexpression was confined to neointimal layers. At 14 days, collagen types I/III were identified in the grafts. The neointima acquired collagen I over time. In the group of animal treated with the LOX inhibitor, intimal hyperplasia was significantly inhibited. Conclusion: LOX were overexpressed in late stages of intimal hyperplasia in the allografts. LOX inhibitors prevented the development of the neointimal layer, such that their modulation could reduce the excessive extracellular matrix deposition that leads to stenosis. Copyright (C) 2010 S. Karger AG, Basel