Plasma Cholesterol Esterification and Plasma Lipoproteins in Bile-duct-ligated Dogs

Abstract

To study the lipoprotein changes in cholestasis while the capacity for plasma cholesterol esterification was normal, the common bile duct was ligated in dogs and plasma investigated 8 h and 48 h later. The plasma concentration of cholesteryl esters was slightly increased, concomitant with a tendency toward an increase in the activity of lecithin: cholesterol acyltransferase (LCAT). The content of cholesteryl esters in the main lipoprotein classes was normal. Marked alteration in the low density lipoproteins (LDL) and the high density lipoproteins (HDL) took place and were essentially similar 8 h and 48 h after bile duct ligation. In LDL₁ (density 1.006–1.019 g/ml) and LDL₂ (density 1.019–1.063 g/ml) an increase in the content of polar lipids was observed, and in LDL₂ heterogeneity in particle size was demonstrated by gelfiltration on 2% agarose and by electron microscopy. Large myelin structures, flattened disc-shaped particles, and particles with the appearance of normal LDL₂ were present. HDL isolated after operation was characterized by a decreased protein/lipid ratio and an increased content of phospholipids. By gelfiltration on Sephadex G-200 and by electron microscopy changes in particle size were observed, with the presence of disc-shaped particles with a tendency to form rouleaux. These results demonstrate that marked lipoprotein changes occur as early as 8 h after bile duct ligation in dogs and indicate that a deficient LCAT mechanism is present in cholestasis even with normal or high plasma LCAT activity.

Key-words:

• Cholesterol acyltransferase
• electron microscopy
• gelfiltration
• lecithin
• lipid composition
• ultracentrifugation