Abstract
We investigated the properties of very low density lipoprotein (VLDL) from two types of Watanabe heritable hyperlipidemic (WHHL) rabbits: one with a high incidence of coronary atherosclerosis (type 1), and the other with a low incidence (type 2). When incubated with mouse peritoneal macrophages, VLDL from type 1 WHHL rabbit (type 1-VLDL) stimulated cholesteryl ester synthesis 10.5-fold more than VLDL from the type 2 WHHL rabbit (type 2-VLDL) did. Moreover, a similar difference was seen in the stimulation of cholesteryl ester synthesis in peritoneal macrophages isolated from the WHHL rabbits. The mass ratios of cholesterol to protein in type 1- and type 2-VLDL were 5.69 and 2.05, respectively. Agarose gel electrophoresis of type 1-VLDL showed beta mobility, and that of type 2-VLDL showed pre-beta mobility. No difference was seen between the sizes of VLDL particles of the two types. The amount of apolipoprotein E in type 1-VLDL was greater than that in type 2-VLDL. In conclusion, the difference between type 1 and type 2 WHHL rabbits is at least partly due to the presence in type 1 animals of VLDL particles rich in cholesteryl esters and apolipoprotein E, particles which are very similar to beta-VLDL in conformation.
Highlights
Cardiovascular Center Research Institute, Suita, Osaka, 565, Japan; and Research Center,tt Mitsubishi Chemical Industries, Ltd., Yokohama, Kanagawa, 227, Japan
We examined the stimulative effects of very low density lipoprotein (VLDL) from type 1 and type 2 Watanabe heritable hyperlipidemic (WHHL) rabbits on cholesteryl ester synthesis in peritoneal macrophages from homozygous WHHL rabbits
The difference observed between these two lipoproteins in the stimulation of cholesteryl ester synthesis was similar to that seen in mouse peritoneal macrophages (Fig. 2)
Summary
Cardiovascular Center Research Institute, Suita, Osaka, 565, Japan; and Research Center,tt Mitsubishi Chemical Industries, Ltd., Yokohama, Kanagawa, 227, Japan. Homozygous Watanabe heritable hyperlipidemic (WHHL) rabbits resemble human hyperlipidemic subjects in having an accumulation of cholesterol-rich particles in very low density lipoprotein (VLDL) and intermediate density lipoprotein classes, as well as in low density lipoproteins when maintained on a low fat diet, tendon xanthomas, severe atherosclerotic lesions of the aorta, and a genetic defect in the LDL receptors of all tissues [1,2,3,4,5,6,7,8] These human subjects die from coronary atherosclerosis between the ages of 3 and 30 years, the incidence of the disease in homozygous WHHL rabbits at an early age (4-12 mon) has been low [9, 10]. In WHHL rabbits, cholesterol-rich VLDL appears to play an important role in atherosclerosis [19]
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