| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1998: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1997: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Research Abstract |
To investigate the occurrence of apoptosis in the atherosclerotic lesion, ascending aortas of the low density lipoprotein receptor knock out (LDL KG) mice were stained with TUNEL methods after the feeding with high cholesterol diet for 6 or 9 months. TUNEL positive cells were observed in the thickened intimas increasing in their number as the lesion progressed. In addition, electron microscopic study confirmed the occurrence of apoptotic change in the foam cells in the atherosclerotic lesions.
To investigate the expression of apoptosis-related proteins in this model, anti-ICE, anti-Bax and anti-Bcl-2 were used to stain the aortas of the LDL KG mice. Although the expression of apoptosis-accelerating proteins, ICE and Bax was unchanged with the disease progression, Bcl-2 was less strongly expressed in the advanced stage than in the earlier stage.
LDL KG mice were given both an accelerator of apoptosis, galic acid, and a inhibitor of apoptosis, ZVAD-fmk intraperitoneally for 8 weeks. However, these systemic administration of these drugs did not significantly increase or decrease the size of atheroma or the number of TUNEL positive cells in the lesions.
As a conclusion, the apoptosis, a programmed cell death acts in the formation of atherosclerosis in this model, and the decrease of the expression of apoptosis-inhibiting protein, Bcl-2 may control the cell death and contribute the progression of atheroma. However, systemic administration of apoptosis controlling agents failed to influence the size or cell components of atherosclerotic lesion.
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