Expression of PCNA and Oxidative Stress Injury with Intimal Hyperplasia in Rabbit Experimental Vein Graft.
- Author:
In Mok JUNG
1
;
Tae Seung LEE
;
Seung Kee MIN
;
Jongwon HA
;
Jung Wook SEO
;
Myung Hee CHUNG
;
Sang Joon KIM
Author Information
1. Department of Surgery and Heart Research Institute, Seoul National University, College of Medicine, Korea.
- Publication Type:Original Article
- Keywords:
Intimal hyperplasia;
PCNA;
Malondialdehyde;
Oxidative stress injury
- MeSH:
Atherosclerosis;
Carotid Arteries;
Cell Proliferation;
Formaldehyde;
Humans;
Hyperplasia*;
Jugular Veins;
Male;
Malondialdehyde;
Models, Theoretical;
Muscle, Smooth, Vascular;
New Zealand;
Nitrogen;
Oxidative Stress*;
Proliferating Cell Nuclear Antigen*;
Reactive Oxygen Species;
Transplants*;
Vascular System Injuries;
Veins*
- From:Journal of the Korean Society for Vascular Surgery
1999;15(1):1-11
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
Proliferation of vascular smooth muscle cells (VSMCs) is the utmost important pathophysiologic mechanism of intimal hyperplasia and atherosclerosis. With a hyperlipidemic rabbit model of jugular vein graft to carotid artery, we invesigated the oxidative stress injury in intimal hyperplasia and correlation of PCNA expression with VSMCs proliferation and intimal hyperplasia. Twenty jugular vein grafts were inserted into the carotid arteries of male New Zealand White rabbit and the vein grafts were harvested at 6 hr, 1 day, 7 days, 14 days, respectively after grafting and rapidly stored in buffered formalin for morphometric analysis, PCNA expression or frozen in liquid nitrogen for MDA (Malondialdehyde) analysis. Total wall and intimal thickness of grafts were measured with an computer digitalized image analyzer. Intimal thickening was rapidly increased at 7 days and peaked at 14 days (125.05 19.80 and 180.25 6.38 mum, respectively) and significantly thicker than control group or 6 hr, 1day after graft implantation (p<0.05). MDA level was significantly higher in vein grafting groups than control group (9.13 1.80 vs. 6.08 1.00 muM/mg protein, p=0.011) by Ohkawa method. In immunohistochemical staining, expression for PCNA (PC10 index: %) in media was peaked at 7 days (12.91 1.22) and significantly higher than control group or 6 hr, 1 day (0, 0.66 0.90, and 3.00 1.22, respectively) after graft implantation (p<0.05) and decreased thereafter. Expression for PCNA (PC10 index) in intima was markedly noted at 7 days (8.60 0.95), peaked at 14 days (16.90 2.14) and significantly higher than control group or 6 hr, 1 day (0, 0.31 0.63, and 1.44 1.00, respectively) after graft implantation (p<0.05). In conclusion, oxidative stress injury by active oxygen species increased in this model of vein graft suggests a role of this oxidant in intimal hyperplasia. PCNA expression was well correlated with the proliferation and migration of VSMCs from media to intima as the pathophysiology of intimal hyperplasia. Therefore, use of PCNA expression in this model of vein graft provides a reproducible method of assessing cellular proliferation after vascular injury. This experimental models of vessel wall injury are helpful in understanding the pathophysiologic mechanism of intimal hyperplasia and are useful in initial assessment of agents intended for reducing intimal hyperplasia.
