The effets of modified LDL's on the interation between foam cells and smooth muscle cells and the distribution of modified LDL's in the liver

• Main Authors: Shian, Jean-may, 沈君玫
• Other Authors: Redman Chu
• Format: Others
• Language: zh-TW
• Published: 1998
• Online Access: http://ndltd.ncl.edu.tw/handle/74625913025805412744

碩士 === 國立臺灣大學 === 獸醫學系研究所 === 86 === AbstractLow-density lipoprotein, especially modified LDL such as oxidized LDL （ox-LDL）, malodialdehyde modified LDL (MDA-LDL) and acetyl-LDL, had been kno wn to play a significant role in the pathogenesis of atherosclerosis. The live r is an important organ for the metabolism of atherogenic lipoproteins, thus, the first part of this study was to determine what kind of the modified LDLs w ere present in this organ, and where these LDLs resided. The differences in th e types of LDLs in the liver and aorta were also investigated. The specimens o f liver and aorta were collected from pigs fed on a high cholesterol diet for 12 weeks; immunohistochemical stains were performed to identify the different of types LDLs. The results showed that LDL and MDA-epitopes were colocalized i n sinusoid and Kupffer's cells in the liver; LDL and MDA epitopes were also ex isted in close vicinity in the neointima of the aorta from specimens of the sa me pigs. However, acetyl-epitope was found in the hepatocytes but was absent i n the aorta. It is therefore indicated that the liver is another candidate for LDL oxidation in the body.Macrophages and smooth muscle cells (SMCs) are two of the major reactive cells in atherosclerosis, a disease characterized by unc ontrolled proliferation of SMCs. The second part of this study was designed to determine, in an in vitro system, the effects of different types of LDL on th e capability of macrophage to modulate SMCs proliferation. In this study, peri toneal macrophages in mice were isolated by intraperitoneal washing with PBS a nd were seeded on 35mm wells of tissue culture plates. The cells were treated with 50μg/ml LDL, ox-LDL, acetyl-LDL, or PBS for 24 hrs. Following wash with PBS, the cells were then incubated for another 2 hrs in fresh medium. The supe rnatant, intact cells and cell debris were cocultured with swine SMCs for 48 h ours. The number of SMCs was then measured. The results showed that the intact macrophages, lysis macrophages in the ox-LDL and acetyl-LDL treated groups si gnificantly stimulate the proliferation of SMCs. It was also noted that the ce ll debris of macrophage had a stronger effect on SMC proliferation. It is conc luded that the ox-LDL or acetyl-LDL laden macrophages play a significant role in the pathogenesis of atherosclerosis. In addition, the effect of disrupted m acrophages on the pathogenesis of this disease should not be ignored.