Korean Circ J.  2004 Jan;34(1):69-75. 10.4070/kcj.2004.34.1.69.

Antioxidants Inhibit Smooth Muscle Cell Proliferation in vitro and Neointimal Hyperplasia in vivo after Carotid Artery Injury in the Rat

• Kim H
• Park CK
• Kim KS

• KMID: 1938856
• DOI: http://doi.org/10.4070/kcj.2004.34.1.69

Abstract

BACKGROUND
Smooth muscle cell proliferation and neointimal hyperplasia are major components in in-stent restenosis. In smooth muscle cells, reactive oxygen species (ROS) have been shown to mediate cell proliferation. We investigated whether antioxidants inhibit smooth muscle cell proliferation and neointimal hyperplasia after carotid artery injury in a rat model.
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.

Keyword

Antioxidants; Myocytes, smooth muscle; Restenosis

MeSH Terms

Acetylcysteine
Animals
Antioxidants*
Arteries
Carotid Arteries*
Carotid Artery Injuries*
Catalase
Cell Count
Cell Proliferation
Hyperplasia*
Microscopy, Confocal
Models, Animal
Muscle, Smooth*
Myocytes, Smooth Muscle*
Rats*
Reactive Oxygen Species
Superoxide Dismutase
Acetylcysteine
Antioxidants
Catalase
Reactive Oxygen Species
Superoxide Dismutase