Abstract
Animals of various species are widely used as models with which to study atherosclerosis and the lipoprotein metabolism. The objective of this study was to investigate the lipoprotein profiles in Wistar rats and New Zealand white rabbits with experimentally induced hyperlipidemia by means of ultracentrifugation. The Schlieren curves were utilized to compare suckling and adult rat sera to determine whether aging causes alterations in lipoprotein profiles. A striking feature of the data is the high concentration of low-density lipoproteins (LDL), (>5.2 mmol/l cholesterol) in the 2-week old rat serum pool which was greatly decreased in the 3-weeks rat serum pool (<1.3 mmol/l cholesterol). Additional experiments were performed to permit a direct comparison of the amounts of lipoprotein present in rat sera in experimental hyperlipidemia post-Triton WR 1339 administration. Rapid changes in concentrations in very low-density lipoproteins (VLDL), LDL and high-density lipoproteins (HDL) were observed after Triton injection. The administration of Triton WR 1339 to fasted rats resulted in an elevation of serum cholesterol levels. Triton physically alters VLDL, rendering them refractive to the action of lipolytic enzymes in the blood and tissues, preventing or delaying their removal from the blood. Whereas the VLDL concentration was increased markedly, those of LDL and HDL were decreased at 20 h after Triton treatment. Rabbits were fed a diet containing 2% cholesterol for 60 days to develop hyperlipidemia and atheromatous aortic plaques. A combination of preparative and analytical ultracentrifugation was used to investigate of LDL aliquots, to prepare radioactive-labeled lipoproteins and to study induced hyperlipidemia in rabbits. Analytical ultracentrifugation was applied to investigate the LDL flotation peaks before and after cholesterol feeding of rabbits. Modified forms of LDL were detected in the plasma of rabbits with experimentally induced atherosclerosis. ApoB-containing particles, migrating as LDL, intermediate density lipoproteins and VLDL were the most abundant lipoproteins. Gamma camera in vivo scintigraphy on rabbits with radiolabeled lipoproteins revealed visible signals corresponding to atherosclerotic plaques of the aorta and carotid arteries.
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References
Back MR, Carew TE, Schmid-Schoenbein GW (1995) Deposition pattern of monocytes and fatty streak development in hypercholesterolemic rabbit. Atherosclerosis 116:103–115
Bocan TM, Mueller SB, Mazur MJ, Uhlendorf PD, Brown EQ, Kieft KA (1993) The relationship between the degree of dietary-induced hypercholesterolemia in the rabbit and atherosclerotic lesion formation. Atherosclerosis 102:9–22
Bozóky Z, Fülöp L, Gy. Jánoki A (2002) Combination of preparative and analytical ultra-centrifugation methods for the investigation of the low density lipoprotein (LDL) aliquots to prepare radioactive labelling lipoproteins. Progr Colloid Polymer Sci Vol 119:43–49
Bozóky Z, Fülöp L, Köhidai L (2001) A short-run new analytical ultracentrifugal micro method for determining low density lipoprotein subfractions using Schlieren refractometry. Eur Biophis J 29(8) 621–627
Brown MS, Goldstein JL (1983) Lipoprotein metabolism in the macrophage: implications for cholesterol deposition in atherosclerosis. Annu Rev Biochem 52:223–261
Brown MS, Goldstein JL (1986) A receptor-mediated pathway for cholesterol homeostasis. Science 232:34–47
Fernando-Warnakulasuriya GJ, Eckerson ML, Clark WA, Wells MA (1983) Lipoprotein metabolism in the suckling rat: characterization of plasma and lymphatic lipoproteins. Lipid Res 24(12):1626–1638
Friedman M, Byers SO (1957) Hypercholesteremia induced by triton WR-1339. Am J Physiol 190:439–445
Ginsberg HN, Goldsmith SJ, Vallabhajosula S (1990) Noninvasive imaging of 99mtechnetium-labeled low density lipoprotein uptake by tendon xanthomas in hypercholesterolemic patients. Arteriosclerosis 10(2):256–262
Hay RV, Fleming RM, Ryan JW, Williams KA, Stark VJ, Lathrop KA, Harper PV (1991) Nuclear imaging analysis of human low-density lipoprotein biodistribution in rabbits and monkeys. J Nucl Med 32(6):1239–1245
Lees AM, Lees RS, Schoen FJ, Isaacsohn JL, Fischman AJ, McKusick KA, Strauss HW (1988) Imaging human atherosclerosis with 99 mTc-labeled low density lipoproteins. Arteriosclerosis 8(5):461–470
Lindgren FT, Jensen LC, Wills RD, Freeman NK (1969) Flotation rates, molecular weights and hydrated densities of the low-density lipoproteins. Lipids 4:337–344
Lupatelli G, Virgolini ILISR, Sinzinger H (1991) Low density lipoprotein receptors: preliminary results on “in vivo” study. Wiener Klin Wochen. 15:462–465
Restori G, Boiardi L, Barbagallo M, Novo S, Passeri M, Strano A (1990) Progression of induced aortic atherosclerosis in rabbits fed a high cholesterol diet. Int Angiol 9:263–265
Swinkels DW, Hak-Lemmers HLM, Demacker PNM (1987) Single spin density gradient ultracentrifugation method for the detection and isolation of light and heavy low density lipoprotein subfractions. J Lipid Res 28:1233–1239
Swinkels DW, Demacker PNM, Hendriks JCM, van ’t Laar A (1989) Low density lipoprotein subfractions and relationship to other risk factors for coronary artery disease in healthy individuals. Arteriosclerosis 9:604–613
Vallabhajosula S, Goldsmith S (1990) 99 mTc-low density lipoprotein: intracellularly trapped radiotracer for noninvasive imaging of low density lipoprotein metabolism in vivo. Semin Nucl Med 1:68–79
Virgolini I, Rauscha F, Lupattelli G, Angelberger P, Ventura A, O’Grady J (1991) Sinzinger H autologous low density lipoprotein labelling allows characterization of human atherosclerotic lesions in vivo as to presence of foam cells and endothelial coverage. Eur J Nucl Med 18:948–951
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Bozóky, Z., Balogh, L., Máthé, D. et al. Evaluation of rat and rabbit sera lipoproteins in experimentally induced hyperlipidemia by analytical ultracentrifugation. Eur Biophys J 35, 205–213 (2006). https://doi.org/10.1007/s00249-005-0022-x
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DOI: https://doi.org/10.1007/s00249-005-0022-x