A.E. La Ville

Modified plasma-derived lipoproteins in human atherosclerotic plaques

Low density lipoproteins extracted from surgical specimens of human atherosclerotic plaques (A-LDL) showed altered electrophoretic mobility indicating a greater negative charge than that of plasma LDL (P-LDL). A-LDL but not P-LDL showed high affinity binding/degradation by human monocyte-derived macrophages; this was inhibited by acetylated LDL but not by native P-LDL. Following injection of 125I-labelled autologous P-LDL prior to reconstructive arterial surgery, polyacrylamide and agarose gel electrophoresis of A-LDL extracted from arterial intima showed that the A-LDL and its apolipoprotein B moiety were derived from P-LDL; the electrophoretic mobility of the product A-LDL was greater than that of native P-LDL. The compositions of arterial intermediate density lipoprotein (A-IDL) and A-LDL differed from those obtained from human plasma intermediate density lipoprotein (P-IDL) and P-LDL. A-IDL showed a reduced triglyceride content and increased esterified and unesterified cholesterol. Although the total cholesterol content of A-LDL was similar to that of P-LDL, there was an increase in unesterified cholesterol and a decrease of cholesteryl ester. These studies indicate that LDL extracted from human atherosclerotic plaque is derived from and modified from P-LDL in vivo. Compared with native P-LDL, A-LDL showed differences in charge and composition, associated with its high affinity binding by the acetyl LDL receptor of human macrophages.

Metabolic studies on the hypolipidaemic effect of guar gum

The hypolipidaemic effect of guar gum (30 g/day) was examined in a double blind placebo-controlled crossover study in 9 patients with primary hyperlipidaemia. The treatment periods were of six weeks duration. Cholesterol levels in low density lipoprotein (LDL) were decreased by 11.5% and in intermediate density lipoprotein (IDL) by 10.7%. Plasma cholesterol levels were reduced by 9.6% (P less than 0.05). Kinetic studies using autologous 125I-labelled LDL showed a decrease of 21.6% in plasma LDL apo B pool size (P less than 0.05) that resulted from a 39.1% increase in its fractional rate of catabolism. The kinetic effects of guar gum on LDL metabolism appear similar to that of bile acid binding resins in that LDL apo B fractional catabolism is greatly increased while there is a slight increase in production rate.

Primary prevention of atherosclerosis by lovastatin in a genetically hyperlipidaemic rabbit strain

Lovastatin, a lipid-lowering drug which inhibits cholesterol synthesis, was administered to genetically hyperlipidaemic rabbits from the age of 2 months. Twenty rabbits were selected with similar plasma cholesterol levels and divided into matched treatment and control groups. The treated animals showed a 60% decrease in plasma cholesterol due to reduced levels of low density lipoprotein (LDL) and intermediate density lipoprotein (IDL). Levels of other lipoproteins remained unchanged. In untreated animals cholesterol levels in plasma, LDL and IDL increased with age. The area of aortic atherosclerosis-like lesions was quantified after 2-10.5 months of treatment. At each time point the extent of arterial disease was profoundly less in treated than in untreated animals. The findings demonstrate that primary prevention of arterial lesions resembling human atherosclerosis (increased amounts of fibrous tissue, smooth muscle cell proliferation, foam cell formation and necrosis at the base of the plaques) results from early effective reduction of elevated plasma lipids by lovastatin in this rabbit strain.