Influx, efflux, and accumulation of LDL in normal arterial areas and atherosclerotic lesions of white Carneau pigeons with naturally occurring and cholesterol-aggravated aortic atherosclerosis.

This study investigated the hypothesis that increased influx of low-density lipoprotein (LDL) accounts for the natural development of atherosclerosis in a characteristic (susceptible) site in the distal thoracic aorta of White Carneau (WC) pigeons and the exacerbation of atherosclerosis by cholesterol feeding. The influence of dietary cholesterol-induced changes in LDL composition on LDL influx into the artery was also investigated. As a measure of the influx of LDL into the artery, we determined the arterial accumulation of radiolabeled LDL after 1 hour. Nine 50-month-old WC pigeons with naturally occurring atherosclerosis and seven 14-month-old WC pigeons with atherosclerosis accelerated by 10 months of cholesterol feeding were studied. In the absence of atherosclerotic lesions, we found no evidence for increased accumulation of LDL at the susceptible site. In fact, more LDL accumulated in less susceptible normal arterial areas near the heart (approximately 90 nl/h per square centimeter) than in the susceptible distal thoracic aorta (approximately 35 nl/h per square centimeter). In the absence of atherosclerotic lesions, LDL accumulation (nanoliters per hour per square centimeter) was not influenced by hypercholesterolemia, although mass transport of LDL cholesterol into the artery was increased. Naturally occurring atherosclerotic lesions accumulated five times as much LDL as the adjacent normal arterial area (P < .001), whereas cholesterol-aggravated atherosclerotic lesions in different arterial sites accumulated four to 26 times as much LDL as the adjacent normal artery (P < .05). Cholesterol-aggravated atherosclerotic lesions at the most susceptible site accumulated five times as much LDL as naturally occurring atherosclerotic lesions in the corresponding arterial site (823 +/- 241 vs 175 +/- 45 nl/h per square centimeter, mean +/- SEM; P < .005). Arterial accumulation of LDL was influenced very little by changes in LDL composition induced by cholesterol feeding. In another study with young WC pigeons free of atherosclerosis and other WC pigeons with cholesterol-aggravated atherosclerosis, we injected differently labeled LDL 0.5 and 1 hour before sacrifice to investigate whether efflux of LDL from the artery was significant during a 1-hour period of LDL uptake. Although efflux of LDL from all arterial sites occurred during 1 hour, differential efflux could not account for regional differences in 1-hour arterial LDL accumulation. This study suggests that the characteristic susceptibility of the distal thoracic aorta of WC pigeons to atherosclerosis and the exacerbation of atherosclerosis by cholesterol feeding cannot be explained by differences in influx or efflux of LDL.(ABSTRACT TRUNCATED AT 400 WORDS)

[1]  R. Tompkins,et al.  Quantitative analysis of blood vessel permeability of squirrel monkeys. , 1991, The American journal of physiology.

[2]  T. Carew,et al.  Initiation of atherosclerotic lesions in cholesterol-fed rabbits. I. Focal increases in arterial LDL concentration precede development of fatty streak lesions. , 1989, Arteriosclerosis.

[3]  T. Carew,et al.  Initiation of atherosclerotic lesions in cholesterol-fed rabbits. II. Selective retention of LDL vs. selective increases in LDL permeability in susceptible sites of arteries. , 1989, Arteriosclerosis.

[4]  D. B. Zilversmit,et al.  The arterial barrier to lipoprotein influx in the hypercholesterolemic rabbit. 2. Long-term studies in deendothelialized and reendothelialized aortas. , 1989, Atherosclerosis.

[5]  S. Stender,et al.  In Vivo Transfer of Cholesteryl Ester from High and Low Density Plasma Lipoproteins into Human Aortic Tissue , 1988, Arteriosclerosis.

[6]  O. Portman,et al.  Metabolism of native and acetylated low density lipoproteins in squirrel monkeys with emphasis on aortas with varying severities of atherosclerosis. , 1987, Atherosclerosis.

[7]  D. B. Zilversmit,et al.  Enhanced Accumulation and Turnover of Esterified Cholesterol in Injured Rabbit Aorta , 1987, Arteriosclerosis.

[8]  D H Blankenhorn,et al.  Beneficial effects of combined colestipol-niacin therapy on coronary atherosclerosis and coronary venous bypass grafts. , 1987, JAMA.

[9]  D. L. Fry,et al.  Mass transport, atherogenesis, and risk. , 1987, Arteriosclerosis.

[10]  S. Ghosh,et al.  Arterial uptake indices of low density lipoproteins after fatty streak formation in Cynomolgus monkeys. , 1987, Cardiovascular research.

[11]  R. Krauss,et al.  Nondenaturing polyacrylamide gradient gel electrophoresis. , 1986, Methods in enzymology.

[12]  H. Barakat,et al.  Characterization of plasma lipoproteins of grain- and cholesterol-fed White Carneau and Show Racer pigeons. , 1985, Journal of lipid research.

[13]  J F Cornhill,et al.  Topographic Study of Sudanophilic Lesions in Cholesterol‐Fed Minipigs by Image Analysis , 1985, Arteriosclerosis.

[14]  T. Carew,et al.  Role of the Low Density Lipoprotein Receptor in Penetration of Low Density Lipoprotein into Rabbit Aortic Wall , 1985, Arteriosclerosis.

[15]  T. Carew,et al.  Measurement in vivo of irreversible degradation of low density lipoprotein in the rabbit aorta. Predominance of intimal degradation. , 1984, Arteriosclerosis.

[16]  D. Steinberg.  Lipoproteins and atherosclerosis. A look back and a look ahead. , 1983, Arteriosclerosis.

[17]  A. Attie,et al.  A radioiodinated, intracellularly trapped ligand for determining the sites of plasma protein degradation in vivo. , 1983, The Biochemical journal.

[18]  N. Simionescu,et al.  Visualization of the binding, endocytosis, and transcytosis of low- density lipoprotein in the arterial endothelium in situ , 1983, The Journal of cell biology.

[19]  S. Stender,et al.  In vivo fluxes of plasma cholesterol, phosphatidylcholine and protein into mini-pig aortic and pulmonary segments. , 1982, Atherosclerosis.

[20]  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.

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

[22]  E. B. Smith,et al.  Distribution of plasma proteins across the human aortic wall--barrier functions of endothelium and internal elastic lamina. , 1980, Atherosclerosis.

[23]  D. L. Fry,et al.  Quantitative microautoradiography of arteries: comparison of radioactivity to silver. , 1980, The American journal of physiology.

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

[25]  W. Wagner,et al.  Blood Pressure in Atherosclerosis-Susceptible and -Resistant Pigeons , 1979, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[26]  Kottke Ba,et al.  Location and sequence of atherosclerotic plaque formation in white Carneau and show racer pigeons: reevaluation and redefinition. , 1978 .

[27]  P. Fraker,et al.  Protein and cell membrane iodinations with a sparingly soluble chloroamide, 1,3,4,6-tetrachloro-3a,6a-diphrenylglycoluril. , 1978, Biochemical and biophysical research communications.

[28]  L. Rudel,et al.  Characterization of plasma low density lipoproteins on nonhuman primates fed dietary cholesterol. , 1977, Journal of lipid research.

[29]  J. Cornhill,et al.  The effect of the duration of cholesterol feeding on the development of sudanophilic lesions in the rabbit aorta. , 1976, Atherosclerosis.

[30]  H. Lofland,et al.  Proline hydroxylase activity and collagen content of pigeon aortas with naturally-occurring and cholesterol-aggravated atherosclerosis. , 1975, Atherosclerosis.

[31]  T. B. Clarkson,et al.  The development of pigeon strains with selected atherosclerosis characteristics. , 1973, Experimental and molecular pathology.

[32]  S. Dayton,et al.  Recent advances in molecular pathology: a review. Cholesterol flux and metabolism in arterial tissue and in atheromata. , 1970, Experimental and molecular pathology.

[33]  U. K. Laemmli,et al.  Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4 , 1970, Nature.

[34]  Montenegro Mr,et al.  Topography of atherosclerosis in the coronary arteries. , 1968 .

[35]  S. Christensen.  TRANSFER OF LABELLED CHOLESTEROL ACROSS THE AORTIC INTIMAL SURFACE OF NORMAL AND CHOLESTEROL-FED COCKERELS. , 1964, Journal of atherosclerosis research.

[36]  H. Lofland,et al.  AORTIC ATHEROSCLEROSIS IN PIGEONS AND ITS COMPLICATIONS. , 1964, Archives of pathology.

[37]  H. Lofland,et al.  MYOCARDIAL INFARCTS IN PIGEONS. , 1963, The American journal of pathology.

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

[39]  J. Cornfield,et al.  The effect of blood pressure on the passage of labeled plasma albumin into canine aortic wall. , 1962, The Journal of clinical investigation.

[40]  W. J. Dyer,et al.  A rapid method of total lipid extraction and purification. , 1959, Canadian journal of biochemistry and physiology.

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

[42]  R. Havel,et al.  The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum. , 1955, The Journal of clinical investigation.

[43]  B. Brodie,et al.  A simplified method for the estimation of total cholesterol in serum and demonstration of its specificity. , 1952, The Journal of biological chemistry.

[44]  O. H. Lowry,et al.  Protein measurement with the Folin phenol reagent. , 1951, The Journal of biological chemistry.