Elevated Concentrations of Plasma Lipids and Apolipoproteins B, C-III, and E Are Associated With the Progression of Coronary Artery Disease in Familial Hypercholesterolemic Swine

Abstract

Abstract We reported earlier that a complex familial hypercholesterolemia (c-FHC) phenotype characterized by elevated levels of total plasma cholesterol (TC) and apoB and reduced levels of HDL cholesterol (HDL-C) and apoA-I is associated with the development of spontaneous atherosclerotic lesions in swine. In this study, we investigated concentrations of plasma lipids and apolipoproteins B, C-III, and E in six parental animals of two cholesterol concentration phenotypes and their 32 offspring, which segregated into high, intermediate, and normal cholesterol phenotypes. Subsequently, we compared the extent of atherosclerotic lesion development in coronary arteries to the concentrations of plasma lipids and apolipoproteins in the parents and two offspring per family. Mean concentrations for the high (n=23), intermediate (n=13), and normal (n=2) cholesterol level phenotypes at 4 months of age were TC, 316±62.2, 159±17.1, and 105±12 mg/dL; LDL cholesterol, 275±63.1, 113±16.4, and 67±18.4 mg/dL; HDL-C, 35±6.1, 41±5.7, and 33±6.4 mg/dL; triglycerides, 48±10.8, 39±8.0, and 29±5.7 mg/dL; apoB, 152±32.5, 80±7.2, and 48±5.7 mg/dL; apoC-III, 10±4.2, 8±1.7, and 3±0.1 mg/dL; and apoE, 17±3.4, 7±1.7, and 5±0.7 mg/dL, respectively. Histological analysis of the major coronary arteries from members of the three families showed considerable variation in the severity of lesions, ranging from foci of adaptive intimal thickening consisting of two to six layers of smooth muscle cells to advanced lesions containing necrotic cores, cholesterol clefts, calcification, and hemorrhage (type V). The most extensive lesions occurred only in animals of the high cholesterol phenotype (ie, c-FHC), in which the concentration of TC and apoB progressively increased after 4 months of age, apoC-III, apoE, and triglycerides increased or remained elevated, and HDL-C decreased, except for one animal. Data presented here show that the plasma cholesterol phenotypes in FHC animals are associated with levels of apolipoproteins B, C-III, and E and indicate that the increases in the studied parameters after 4 months of age correlate with the progression of coronary artery disease.