METHODS: Rat aortic smooth muscle cells were stimulated by PDGF (80 ng/mL) with or without N-acetylcysteine (NAC) 1 mM. Intracellular ROS levels were measured by carboxyl-2', 7'-dichlorodihydrofluorescein diacetate confocal microscopy, and cellular proliferation was evaluated by cell counting and XTT assay. Rat carotid arteries were injured with a balloon and with NAC 100 mM, pyrrolidinedithiocarbamate (PDTC) 100 uM, catalase 5000 u/mL, or superoxide dismutase (SOD) 2,000 u/mL. All agents were applied in pluronic gel on the periadventitial side of the injured artery. At 21 days after, the intima/media (I/M) ratios were measured.

RESULTS: In rat aortic smooth muscle cells culture, NAC inhibited PDGF-induced increase of ROS by 77% and PDGF-induced cellular growth by 45%. In balloon injured rat carotid artery, PDTC showed the most prominent effect and reduced the I/M ratio by 51% (0.94±0.32 vs. 1.96±0.14, p<0.05) versus the control. Catalase, SOD, and NAC treatments also reduced the I/M ratio (1.08±0.43, 1.30±0.31, 1.43±0.34, respectively, versus the control (1.96±0.14), all p<0.05).

CONCLUSION: Antioxidant treatment may inhibit the proliferation of RASMC stimulated by PDGF by reducing intracellular ROS in vitro and neointimal hyperplasia after balloon injury to the rat carotid artery.