Effect of Human Bcl-2 Gene Expression on the Peripheral Atherosclerotic Lesions of Apolipoprotein E-Deficient Mouse

Park, Sang Weon; Seo, Hong Seog; Kim, Jin Won; Hong, Soon Jun; Shin, Sung Hee; Rha, Seung Woon; Ahn, Jeong Cheon; Song, Woo Hyuk; Park, Chang Gyu; Shim, Wan Joo; Oh, Dong Joo; Ro, Young Moo

Abstract

BACKGROUND AND OBJECTIVES
Bcl-2 protein is related to the inhibition of apoptosis via the mitochondrial pathway and Bcl-2's anti-oxidant effect. During the development of atherosclerosis, apoptosis is known to play an important role in the pathophysiologic behavior of atherosclerotic vascular disease in the medium-sized arteries. Apoptosis may be a compensatory reaction to regulate the cellular density of various tissues during the cellular proliferation process such as happens with tissue injury and during the development of atherosclerosis. The consequences of apoptosis in atherosclerosis may be related to the formation of an acellular lipid core, plaque instability and the loss of vascular wall integrity and remodeling. We sought to determine the effect of Bcl-2 gene expression on the development of primary atherosclerosis in apolipoprotein E deficient mouse, which is one of the typical animal models that are used for the development of peripheral atherosclerosis.
MATERIALS AND METHODS
Bcl-2 transgenic mice were cross hybridized with apolipoprotein E deficient mice. Systemic analysis of the distribution and severity of their atherosclerotic lesions was done by dissecting microscopy, and the histological characteristics of the lesions were evaluated in normal chow-fed, 9-month-old apolipoprotein-E deficient/Bcl-2 transgenic mice (n=6) and apolipoprotein-E deficient mice (n=6).
RESULTS
The distribution and severity of atherosclerotic lesions at the peripheral arteries were less in the apolipoprotein-E deficient/Bcl-2 transgenic mice. Acellular lipid core formation, destruction of the smooth muscle cell layers in the media and infiltration of inflammatory cells in the adventitia were much less in the apolipoprotein-E deficient/Bcl-2 transgenic mice. The lipid profile was similar in both groups.
CONCLUSION
The effect of Bcl-2 gene expression on the peripheral atherosclerosis was related with the inhibition or the delay of atherosclerotic lesion progression, such as the reduction of amount of the acellular lipid core, maintenance of vascular smooth muscle cell integrity and the reduction of adventitial inflammation, and this was achieved regardless of serum cholesterol level.