Effects of LDL and Oxidized LDL on Mesangial Cell Proliferation and ICAM-1 Expression

Park, Wondo; Kim, Young Hoon; Park, Jae Kyung; Hong, Sung Pyo; Ahn, Jae Hyung; Lee, Tae Won; Ihm, Chun Gyoo; Kim, Myung Jae

Abstract

OBJECTIVES
As one of the studies for the contribution of hyperlipidemia to the pathogenesis of glomerulosclerosis, this study was performed to evaluate the effects of low density lipoprotein(LDL) and oxidized LDL on mesangial cell proliferation and intercellular adhesion molecule-1 (ICAM-1) expression.
METHODS
Oxidized-LDL and cell-treated LDL were prepared from LDL by incubation with copper sulfate and mesangial cells, respectively. They were each co-incubated with human mesangial cells. The effects of LDL, oxidized-LDL and cell-treated LDL on mesangial cell proliferation were estimated by measuring the uptake of [3H]-thymidine and counting the cell numbers under phase contrast microscopy. The expression of ICAM-1 on mesangial cells was examined by indirect immunofluorescence method.
RESULTS
LDL increased the uptake of [3H]-thymidine by mesangial cells at 10 g/mL returning to control levels at 50 g/mL, and decreased [3H]-thymidine uptake at 100 g/mL of LDL concentration. Also, mesangial cell numbers decreased at 100 g/mL of LDL concentration. In contrast, oxidized LDL decreased [3H]-thymidine uptake starting at 1 g/mL, and decreased mesangial cell numbers starting at 10 g/mL of oxidized-LDL concentration, in a concentration-dependent manner. Cell-treated LDL above the concentration of 10 g/mL caused a concentration- dependent increase in [3H]-thymidine uptake. LDL at certain concentrations increased mesangial cell ICAM-1 expression.
CONCLUSION
These results that low concentration of LDL stimulate and high concentration of LDL and oxidized LDL inhibit human mesangial cell proliferation may be the in vitro evidence of lipid mediated glomerulosclerotic injury.