Canine Lipoproteins and Atherosclerosis

Abstract

Characterization of the hyperlipoproteinemia induced by feeding high-cholesterol diets to hypothyroid dogs was undertaken in an attempt to identify a lipoprotein pattern or a specific lipoprotein responsible for the atherosclerosis associated with such hyperlipoproteinemia. Various degrees of hyperlipidemia and atherosclerosis were produced during the diet, which was imposed for 3 months to more than a year. Dogs referred to as hyporesponders did not develop significant atherosclerosis despite plasma cholesterol levels ranging from two to five times normal or up to 750 mg/100 ml. This nonatherogenic hyperlipidemia was characterized by an increase in the LDL (low density lipoprotein) and HDL_c classes (HDL_c refers to a broad spectrum of cholesterol-enriched particles which resemble high density lipoproteins). Dogs referred to as hyperresponders developed significant and often complicated atherosclerosis. Their plasma cholesterol levels were in excess of 750 mg/100 ml, and most of the increased cholesterol was present in lipoproteins with density less than 1.006 g/ml. Several classes of lipoproteins were isolated by ultracentrifugation and purified by Geon-Pevikon block electrophoresis. These lipoproteins were characterized with respect to chemical composition, electrophoretic mobility, immunochemical reactivity, electron microscopic size after negative staining, and apoprotein content as determined by polyacrylamide gel electrophoresis. We concluded that the atherogenic hyperlipidemia of the hyperresponders was characterized by an increase in the amount of cholesterol-rich HDL_c as in the hyporesponders but was distinguished by the appearance of a spectrum of cholesterol-rich lipoproteins in the fraction with a density less than 1.006 g/ml. One of these cholesterol-rich lipoproteins had the properties of β very low density lipoproteins, and the others had those of HDL^c. We suggest that the spectrum of lipoproteins with density less than 1.006 g/ml represents "remnants" that accumulate because of defective catabolism of lipoproteins synthesized to carry excess of dietary cholesterol.