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Joe, Lim, Jin, and Kim: Effect of Udenafil on Vascular Smooth Muscle Cell Proliferation and Neointimal Hyperplasia in Rat Carotid Artery Injury Model
Original Article
Korean Circulation Journal

Korean Circulation Journal 2008; 38(6): 320-324.

Published online: 30 June 2008

DOI: https://doi.org/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

Jun Ho Joe1, Kwang Suk Lim2, Ji Yong Jin, MD3, Kyung Soo Kim, MD1, 3

1Department of Biomedical Sciences, College of Medicine, Hanyang University, Seoul, Korea.

2Department of Bioengineering, College of Medicine, Hanyang University, Seoul, Korea.

3Division of Cardiology, Department of Internal Medicine, College of Medicine, Hanyang University, Seoul, Korea.

Correspondence: Kyung Soo Kim, MD, Division of Cardiology, Department of Internal Medicine, College of Medicine, Hanyang University, 17 Haengdang-dong, Seongdong-gu, Seoul 133-791, Korea. Tel: 82-2-2290-8312, Fax: 82-2-2298-9183, kskim@hanyang.ac.kr

Received 12 February 2008       Revised 27 March 2008       Accepted 27 March 2008

Copyright © 2008 The Korean Society of Cardiology

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 µM, 10 µM, 1 µM 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 µM, 10 µM and 1 µM) 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 µM 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.

Keywords: Udenafil, Neointimal hyperplasia, Smooth muscle cell

Figures and Tables

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.
kcj-38-320-g001
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.
kcj-38-320-g002
Table 1
Quantitative histomorphological analysis of the rat carotid artery obtained 21 days after the carotid artery injury
kcj-38-320-i001

*Vs control, †Vs 10 µM, ‡Vs 1 µM, p<0.05

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