Urokinase plasminogen activator enhances neointima growth and reduces lumen size in injured carotid arteries

Objectives Increases in urokinase plasminogen activator (uPA) have been rep orted in tissues undergoing remodelling, but its effects on the vessel inti ma formation are not known, We investigated its effects on carotid artery i ntima, media and lumen size, as well as smooth muscle cell (SMC) proliferat ion and migration in vivo. Design and methods Carotid arteries of rats were distended with an inflated balloon catheter and uPA, or uPA-neutralizing antibodies were applied peri vascularly in pluronic gel; control rats received vehicle, Carotid artery s tructure, cell migration and proliferation were assessed after 4 days by qu antitative morphometry and immunohistochemistry. Results Four days after increasing vessel uPA, the intima/ media ratio was double compared to that in control rats (both P < 0.05). The size of the lu men reduced by 75%, compared to the vehicle-treated vessels (P < 0.05). The elevation in uPA also increased SMC numbers in the intima and media, compa red to the vehicle-treated vessels (both P < 0.05). Antibody neutralizing e ndogenous uPA attenuated the growth responses in the distended arteries, re duced neointimal SMC numbers by approximately 50% and prevented much of the reduction in lumen size. Conclusions Thus, local increases in uPA in distended, injured arteries aug ment SMC migratory and proliferative responses, leading to increases in the thickness of the carotid artery intima and media and a reduction in lumen size; effects at least partially attributable to its proteolytic properties . J Hypertens 2000, 18:1065-1069 (C) Lippincott Williams & Wilkins.