Macrophages modify beta-VLDL by proteolysis and enhance subsequent lipid accumulation in arterial smooth muscle cells.

Murine resident peritoneal macrophages (MRPM), incubated with beta-very low density lipoprotein (beta-VLDL), modify the beta-VLDL, producing an increase in the mobility of the lipoprotein. The modification does not result in an increase of thiobarbituric acid-reactive substances (TBARS) in the lipoprotein, and is not inhibited by butylated hydroxyanisole (BHA), EDTA, removal of copper and iron from the medium, or by diphenyliodonium (DPI), suggesting that the mechanism of modification is independent of oxidation. Macrophage conditioned medium performed the modification in the absence of cells, and phenylmethylsulphonyl fluoride (PMSF) inhibited beta-VLDL modification, whereas other protease inhibitors did not, suggesting that a secreted neutral serine protease may possibly be involved in the mechanism. The modified beta-VLDL enhanced the accumulation of cholesterol esters by smooth muscle cells (SMC).