Growth Factor mRNA Expression in Intimal Hyperplasia after Endothelial Denudation
- Author:
Suk In JUNG
1
;
Min Young CHO
;
Sang Yong CHOI
;
Dae Ryong CHA
;
Won Yong CHO
;
Hyoung Kyu KIM
;
Young Sik KIM
;
Bom Woo YEOM
;
Cheung Wung WHANG
Author Information
1. Department of Surgery, Korea University College of Medicine, Korea.
- Publication Type:Original Article
- Keywords:
Intimal hyperplasia;
PDGF;
TGF-beta;
Heparin;
ACE inhibitor
- MeSH:
Animals;
Aorta;
Blood Vessels;
Catheters;
Constriction, Pathologic;
Down-Regulation;
Gene Expression;
Heparin;
Hyperplasia;
Models, Animal;
Myocytes, Smooth Muscle;
Polymerase Chain Reaction;
Ramipril;
Rats;
Reverse Transcription;
RNA, Messenger;
Transforming Growth Factor beta;
Up-Regulation;
Vascular System Injuries
- From:Journal of the Korean Society for Vascular Surgery
1998;14(1):9-17
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
Intimal hyperplasia is the universal response to endothelial denudation and occur after a variety of vascular procedures. In a proportion of cases the smooth muscle cell proliferation may lead to stenosis of the blood vessels. The precise pathophysiologic pathways leading to the development of intimal hyperplasia have not been characterized. This study was undertaken to examine the effect of drugs on the development of proliferative intimal lesion after experimental arterial injury in a rat model. Aortic denudation was performed by balloon catheter in 20 rats. The rats were divided into three group: 1) control group, normal feeding, 2) heparin group, heparin 1200 U/kg/day subcutaneously, 3) ACE inhibitor group, ramipril 10 mg/kg/day subcutaneously. The rat were sacrificed and aortas were perfused and fixed at 21 days after denudation. Microscopic findings were observed and cross sectional intima-to-media ratio were calculated. To evaluate the effects of various drugs on gene expression of aortic smooth muscle cell, semiquantitative reverse transcription polymerase chain reaction(RT-PCR) was done. After reverse transcription, PCR was done to evaluate the change of gene expression in platelet-derived growth factor(PDGF-B), transforming growth factor-beta(TGF-beta). The results were as follows: 1) Normal aorta with intima to media ratio was 0.38+/-0.06. 2) Marked intimal thickening with a mean I-M ratio of 1.35+/-0.45 in the control group. 3) In contrast, the I-M ratio in the heparin group was 0.54+/-0.23, ramipril group was 0.71+/-0.27(P<0.05). 4) mRNA expression of PDGF-B did show significantly increased in control group compared to normal group(0.97+/-0.34 vs 1.60+/-0.21), treatment with heparin and ACE inhibitor shows a tendency to downregulation of mRNA expression to control group(1.04+/-0.31 in heparin group, 1.23+/-0.41 in ACE inhibitor treated group). 5) mRNA expression of TGF-beta was decreased in control group compared to normal group(2.80+/-0.74 vs 1.97+/ 0.24), treatment with heparin and ACE inhibitor shows a tendency to downregulation of mRNA expression to control group(1.36+/-0.40 in heparin group, 1.65+/- 0.45 in ACE inhibitor treated group). In summary, this study shows that repair in even the simplest model of vascular injury is an exceedingly complex, including upregulation of PDGF gene expression. Treatment with heparin and ACE inhibitor revealed a downregulation of each mRAN expression to control group. There results suggest that dysregulation of there gene expression may be involved in the pathogenesis of intimal hyperplasia after endothelial injury.
