Lipid Composition of Aorta of Watanabe Heritable Hyperlipemic and Comparably Hypercholesterolemic Fat‐fed Rabbits: Plasma Lipid Composition Determines Aortic Lipid Composition of Hypercholesterolemic Rabbits

Aortic and plasma lipid compositions were compared during a 12-month period in Watanabe heritable hyperlipemic (WHHL), comparably hypercholesterolemic fat-fed, and age-matched control normolipidemic rabbits to determine whether exposure to equivalent degrees of endogenous or exogenous hypercholesterolemia led to differences in the composition and concentration of lipids deposited in the artery wall. Although there were marked differences in the distribution of cholesterol among the Iipoproteins in the WHHL versus the fat-fed rabbits, the contents of both free and esterified cholesterol were elevated to an equivalent degree in the aorta and plasma. In contrast, the trigiyceride content of both the plasma and aorta were elevated only in the WHHL rabbits. However, aortic total phospholipids were increased in both the WHHL and fat-fed animals as compared to control rabbits. In the control rabbits, there was an agedependent enrichment in aortic relative to plasma cholesteryl-oleate consistent with low density Iipoprotein (LDL) receptor-directed intracellular cholesteryl ester processing. In contrast, enrichment in cholesteryloleate in aortae relative to plasma was not detected in either WHHL or fat-fed groups, suggesting that the plasma cholesteryl ester composition was the primary determinant of the aortic cholesterol composition. Thus, during chronic hypercholesterolemia, deposition of lipids in the artery wall appears to be determined by plasma Iipoprotein levels and composition if the LDL receptor is either absent on a genetic basis or suppressed due to a high-fat, high-cholesterol diet.

[1]  A. Gotto,et al.  Apolipoprotein B Retention in the Grossly Normal and Atherosclerotic Human Aorta , 1977, Circulation research.

[2]  R. S. St. Clair Atherosclerosis regression in animal models: current concepts of cellular and biochemical mechanisms. , 1983, Progress in cardiovascular diseases.

[3]  D. B. Zilversmit,et al.  The effect of cholesterol on the turnover of lecithin, cephalin and sphingomyelin in the rabbit. , 1956, Archives of biochemistry and biophysics.

[4]  G. Odland,et al.  A comparison of cholesterol-ester fatty acid patterns in the blood and in evolving xanthoma and atheroma during cholesterol-feeding of rabbits. , 1966, The Journal of investigative dermatology.

[5]  J. Folch,et al.  A simple method for the isolation and purification of total lipides from animal tissues. , 1957, The Journal of biological chemistry.

[6]  Y. Tsujita,et al.  WHHL‐Rabbit: a low density lipoprotein receptor‐deficient animal model for familial hypercholesterolemia , 1980, FEBS letters.

[7]  S. Hora Statistical Inference Based on Ranks , 1986 .

[8]  D. B. Zilversmit,et al.  ACCUMULATION OF LIPID AND NONLIPID CONSTITUENTS IN RABBIT ATHEROMA. , 1964, Journal of atherosclerosis research.

[9]  R. Clair Atherosclerosis regression in animal models: current concepts of cellular and biochemical mechanisms. , 1983 .

[10]  Y. Watanabe Serial inbreeding of rabbits with hereditary hyperlipidemia (WHHL-rabbit). , 1980, Atherosclerosis.

[11]  M. Brown,et al.  Lipoprotein metabolism in the macrophage: implications for cholesterol deposition in atherosclerosis. , 1983, Annual review of biochemistry.

[12]  A. Chait,et al.  Autoregulation of the Modified Low Density Lipoprotein Receptor in Human Monocyte‐Derived Macrophages , 1982, Arteriosclerosis.

[13]  A. N. Klimov,et al.  Uptake of Intact Plasma Lipoproteins into the Arterial Wall of the Rabbit , 1974 .

[14]  T. Kita,et al.  Cellular Pathology of Progressive Atherosclerosis in the WHHL Rabbit: An Animal Model of Familial Hypercholesterolemia , 1983, Arteriosclerosis.

[15]  B Buis,et al.  Diet, lipoproteins, and the progression of coronary atherosclerosis. The Leiden Intervention Trial. , 1985, The New England journal of medicine.

[16]  M. Brown,et al.  Binding site on macrophages that mediates uptake and degradation of acetylated low density lipoprotein, producing massive cholesterol deposition. , 1979, Proceedings of the National Academy of Sciences of the United States of America.

[17]  T. Kita,et al.  Deficiency of low density lipoprotein receptors in liver and adrenal gland of the WHHL rabbit, an animal model of familial hypercholesterolemia. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[18]  D. Bilheimer,et al.  Impaired receptor-mediated catabolism of low density lipoprotein in the WHHL rabbit, an animal model of familial hypercholesterolemia. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[19]  R. Havel,et al.  Concentration and Composition of Lipoproteins in Blood Plasma of the WHHL Rabbit , 1982, Arteriosclerosis.

[20]  D. B. Zilversmit,et al.  Fatty Acid Composition of Serum and Aortic Intimal Lipids in Rabbits Fed Low‐ and High‐Cholesterol Diets , 1961 .

[21]  G. Odland,et al.  Evidence for the chylomicron origin of lipids accumulating in diabetic eruptive xanthomas: a correlative lipid biochemical, histochemical, and electron microscopic study. , 1970, The Journal of clinical investigation.

[22]  S. Kelsey,et al.  The influence of changes in lipid values induced by cholestyramine and diet on progression of coronary artery disease: results of NHLBI Type II Coronary Intervention Study. , 1984, Circulation.

[23]  M. Traber,et al.  Low density lipoprotein receptor activity in human monocyte-derived macrophages and its relation to atheromatous lesions. , 1980, Proceedings of the National Academy of Sciences of the United States of America.

[24]  M. Wahlqvist,et al.  Incorporation of Oleic Acid into Lipid by Foam Cells in Human Atherosclerotic Lesions , 1969, Circulation research.

[25]  E. B. Smith,et al.  The relationship between plasma and tissue lipids in human atherosclerosis. , 1974, Advances in lipid research.

[26]  M. Brown,et al.  Use of monoclonal anti-receptor antibodies to probe the expression of the low density lipoprotein receptor in tissues of normal and Watanabe heritable hyperlipidemic rabbits. , 1984, The Journal of clinical investigation.

[27]  A. J. Day,et al.  Incorporation of (14C)oleic acid into lipid by foam cells and by other fractions separated from rabbit atherosclerotic lesions. , 1970, Atherosclerosis.

[28]  D. B. Zilversmit,et al.  Uptake and Release of Cholesterol by Rabbit Atheromatous Lesions , 1966, Circulation research.

[29]  O. Portman Arterial composition and metabolism: esterified fatty acids and cholesterol. , 1970, Advances in lipid research.

[30]  R. Lees,et al.  The distribution of labeled low-density lipoproteins across the rabbit thoracic aorta in vivo. , 1977, Atherosclerosis.

[31]  D. Sharpe,et al.  The plasma and tissue turnover and distribution of two radio-iodine-labelled pig plasma low density lipoproteins. , 1975, Atherosclerosis.

[32]  R. Clair Cholesteryl ester metabolism in atherosclerotic arterial tissue. , 1976 .

[33]  E. B. Smith,et al.  Relationship between low-density lipoprotein in aortic intima and serum-lipid levels. , 1972, Lancet.

[34]  M. Brown,et al.  Saturation and suppression of hepatic lipoprotein receptors: a mechanism for the hypercholesterolemia of cholesterol-fed rabbits. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[35]  P. Edwards,et al.  Receptor-mediated uptake of remnant lipoproteins by cholesterol-loaded human monocyte-macrophages. , 1985, The Journal of biological chemistry.

[36]  R. Ross,et al.  Studies of Hypercholesterolemia in the Nonhuman Primate: I. Changes that Lead to Fatty Streak Formation , 1984, Arteriosclerosis.

[37]  D. B. Stein,et al.  Rapid semi-micro procedure for estimating free and total cholesterol. , 1959, Clinical chemistry.

[38]  D. B. Zilversmit,et al.  Arterial influx of esterified cholesterol from two plasma lipoprotein fractions and its hydrolysis in vivo in hypercholesterolemic rabbits. , 1981, Atherosclerosis.

[39]  V. Schumaker Cholesterolemic rabbit lipoproteins: serum lipoproteins of the cholesterolemic rabbit. , 1955, The American journal of physiology.

[40]  D. B. Zilversmit,et al.  Quantitative aspects of cholesterol flux in rabbit atheromatous lesions. , 1962, The Journal of biological chemistry.

[41]  S. Siegel,et al.  Nonparametric Statistics for the Behavioral Sciences , 2022, The SAGE Encyclopedia of Research Design.

[42]  J. Heider,et al.  The picomole determination of free and total cholesterol in cells in culture. , 1978, Journal of Lipid Research.

[43]  G. R. Bartlett Colorimetric assay methods for free and phosphorylated glyceric acids. , 1959, The Journal of biological chemistry.

[44]  A. Gown,et al.  Fatty streak expansion and maturation in Watanabe Heritable Hyperlipemic and comparably hypercholesterolemic fat-fed rabbits. , 1987, Arteriosclerosis.

[45]  H. Kothari,et al.  Arterial enzymes of cholesteryl ester metabolism. , 1978, Advances in lipid research.

[46]  A. Gown,et al.  Fatty streak initiation in Watanabe Heritable Hyperlipemic and comparably hypercholesterolemic fat-fed rabbits. , 1987, Arteriosclerosis.

[47]  D. B. Zilversmit,et al.  Transfer of Plasma Lipoprotein Components and of Plasma Proteins into Aortas of Cholesterol‐Fed Rabbits , 1981, Arteriosclerosis.

[48]  E. Schwenk,et al.  Deposition of Cholesterol in Experimental Rabbit Atherosclerosis.∗ , 1960, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[49]  W. R. Morrison,et al.  PREPARATION OF FATTY ACID METHYL ESTERS AND DIMETHYLACETALS FROM LIPIDS WITH BORON FLUORIDE--METHANOL. , 1964, Journal of lipid research.

[50]  R. Gerrity,et al.  Quantitation of apolipoprotein B in aortas of hypercholesterolemic swine. , 1983, Laboratory investigation; a journal of technical methods and pathology.