Abstract
It is reported that cholesterol ester (CE) deposition was accerelated by acetylated low density lipoprotein (acetyl LDL). To clarify the mechanism of CE deposition by denatured LDL, metabolism of cholesterol ester in reconstituted LDL (rLDL-CE) or acetylated rLDL (acetyl rLDL-CE) was investigated using particulated fraction of rat arterial wall or homogenates of rat peritoneal macrophages.
Hydrolytic activity of rLDL-CE and acetyl rLDL-CE was mainly located in lysosomal fraction. Arterial wall and macrophages were shown to hydrolyse acetylated rLDL-CE in preference to rLDL-CE. So, it is unlikely that CE deposition in acetylated LDL is attributable to deficiency of CE hydrolytic activity in lysosomes.
Next, CE synthesis in microsomes was investigated as a cause of CE deposition. CE synthesis in microsomes from free cholesterol produced by CE hydrolysis in lysosomes was examined. 3H-cholesteryl oleate incorporated rLDL was incubated with macrophage homogenates at pH 4.5, and then [1-14C]oleoyl-CoA was added and further incubation was performed at pH7.5. Although CE hydrolysis was higher in acetyl rLDL-CE than in rLDL, CE synthesis in the case of acetyl rLDL was remarkably higher than that of rLDL. It might be concluded that CE synthesis in microsomes surpass CE hydrolysis in lysosomes because of unknown mechanisms in the case of acetylated LDL.
