Korean Circ J.  2008 Jun;38(6):320-324. 10.4070/kcj.2008.38.6.320.

Effect of Udenafil on Vascular Smooth Muscle Cell Proliferation and Neointimal Hyperplasia in Rat Carotid Artery Injury Model

• Joe JH
• Lim KS
• Jin JY
• Kim KS

• KMID: 2225779
• DOI: http://doi.org/10.4070/kcj.2008.38.6.320

Abstract

BACKGROUND AND OBJECTIVES: Neointimal hyperplasia, which was caused by smooth muscle cell proliferation, was noted to occur after performing percutaneous coronary intervention. Phosphodiesterase type 5 (PDE5) inhibitor has been shown to inhibit smooth muscle cell proliferation. Udenafil is one of the PDE5 inhibitors, and it is also expected to inhibit smooth muscle cell proliferation and reduce neointimal hyperplasia. We investigated the effect of udenafil on the smooth muscle cell proliferation and neointimal hyperplasia that occurs after balloon injury in the carotid arteries of rats.
MATERIALS AND METHODS
Smooth muscle cells were treated with 1 mM, 100 micrometer, 10 micrometer, 1 micrometer and 100 nM concentrations of udenafil. The viability of the smooth muscle cells was evaluated by MTT assay. The carotid arteries of rats were injured with a balloon catheter. Udenafil (100 micrometer, 10 micrometer and 1 micrometer) was applied on the carotid artery adventitia after balloon injury. At 21 days after treatment, the carotid arteries were harvested and stained with H & E. The neointima and media area were measured with a computerized image analysis program.
RESULTS
In the in vitro experiment, treatment with 1 mM udenafil reduced smooth muscle cell viability by 68.8+/-4.42% compared to the control group. In the balloon injured rat carotid artery, treatment with 100 micrometer udenafil reduced the neointima area by 71.8% compared to the control group.
CONCLUSION
Udenafil administration effectively inhibited smooth muscle cell proliferation and it reduced neointimal hyperplasia in the balloon-injured rat carotid artery.

Keyword

Udenafil; Neointimal hyperplasia; Smooth muscle cell

MeSH Terms

Adventitia
Animals
Carotid Arteries
Carotid Artery Injuries
Catheters
Cell Proliferation
Hyperplasia
Muscle, Smooth, Vascular
Myocytes, Smooth Muscle
Neointima
Percutaneous Coronary Intervention
Phosphodiesterase 5 Inhibitors
Pyrimidines
Rats
Sulfonamides
Phosphodiesterase 5 Inhibitors
Pyrimidines
Sulfonamides

Figure

• 

  Fig. 1 MTT assay for the cell viability with using different udenafil concentrations. Quantification of HASMC proliferation was performed with MTT assay in presence of different concentrations of udenafil. *Vs control, †Vs 10 µM, ‡Vs 1 µM, §Vs 100 nM, p<0.05. HASMC: humen artery vascular smooth muscle cell.

• 

  Fig. 2 Histology analysis of the carotid artery. A: control, 100×. B: control, 400×. C: 1 uM udenafil, 100×. D: 1 uM udenafil, 400×. E: 10 uM udenafil, 100×. F: 10 uM udenafil, 400×. G: 100 uM udenafil, 100×. H: 100 uM udenafil, 400×. The bars of the graph represent the neointima area and media area and the neointima/media ratio. *Vs control, †Vs 10 uM, ‡Vs 1 uM, p<0.05. N/M: neointima/media.

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