Depolymerized holothurian glycosaminoglycan (DHG) prevents neointimal formation in balloon-injured rat carotid artery

The in vivo activity of depolymerized holothurian glycosaminoglycan (DHG), a newly developed polysaccharide anticoagulant, on neointimal formation induced by a balloon catheter in the left common carotid artery of rats was investigated. In every Sprague-Dawley rat weighing approximately 400 g, a Forgaty 2Fr balloon catheter was inserted from the left femoral artery to the left common carotid artery, and was passed through three times in order to denude the endothelium of the artery. These rats were divided into four groups by the following treatment protocols; DHG was given to rats by daily subcutaneous injection into their abdomens at a dose of 3 mg/kg or 10 mg/kg (D3 or D10 group). For controls, 250 microl saline was injected daily (C group). Furthermore, 1 mg/kg of unfractionated heparin was also injected daily as a comparison to DHG (H group). Each treatment was performed in six rats, and the injections were continued for two weeks after the catheterization. The area ratio of thickened intima/media (I/M ratio) treated with DHG decreased in a dose-dependent manner compared to the control. In addition, the ratio in the D10 group was significantly lower than in the control (P < 0.01). However, the ratio in the H group did not decrease. By anti-a smooth muscle actin antibody staining the intimal thickening layers were seen to be completely occupied by proliferated smooth muscle cells, and their amount in these layers was attenuated by the DHG treatment. This indicated that DHG has an inhibitory effect on intimal thickening induced by balloon catheterization, and that this might be due to the inactivation of aberrant smooth muscle cells by this agent.