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Diet-induced hyperlipoproteinemia and atherosclerosis in apolipoprotein E3-Leiden transgenic mice.
J Clin Invest. 1994 Apr; 93(4):1403-10.JCI

Abstract

Apolipoprotein E3-Leiden (APOE*3-Leiden) transgenic mice have been used to study the effect of different cholesterol-containing diets on the remnant lipoprotein levels and composition and on the possible concurrent development of atherosclerotic plaques. On high fat/cholesterol (HFC) diet, the high expressing lines 2 and 181 developed severe hypercholesterolemia (up to 40 and 60 mmol/liter, respectively), whereas triglyceride levels remained almost normal when compared with regular mouse diet. The addition of cholate increased the hypercholesterolemic effect of this diet. In lines 2 and 181, serum levels of apo E3-Leiden also increased dramatically upon cholesterol feeding (up to 107 and 300 mg/dl, respectively). In these high expressing APOE*3-Leiden transgenic mice, the increase in both serum cholesterol and apo E3-Leiden occurred mainly in the VLDL/LDL-sized fractions, whereas a considerable increase in large, apo E-rich HDL particles also occurred. In contrast to the high expressing lines, the low expressing line 195 reacted only mildly upon HFC diet. On HFC diets, the high expresser APOE*3-Leiden mice developed atherosclerotic lesions in the aortic arch, the descending aorta, and the carotid arteries, varying from fatty streaks containing foam cells to severe atherosclerotic plaques containing cholesterol crystals, fibrosis, and necrotic calcified tissue. Quantitative evaluation revealed that the atherogenesis is positively correlated with the serum level of cholesterol-rich VLDL/LDL particles. In conclusion, with APOE*3-Leiden transgenic mice, factors can be studied that influence the metabolism of remnant VLDL and the development of atherosclerosis.

Authors+Show Affiliations

TNO Institute of Ageing and Vascular Research, Gaubius Laboratory, Leiden, The Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

8163645

Citation

van Vlijmen, B J., et al. "Diet-induced Hyperlipoproteinemia and Atherosclerosis in Apolipoprotein E3-Leiden Transgenic Mice." The Journal of Clinical Investigation, vol. 93, no. 4, 1994, pp. 1403-10.
van Vlijmen BJ, van den Maagdenberg AM, Gijbels MJ, et al. Diet-induced hyperlipoproteinemia and atherosclerosis in apolipoprotein E3-Leiden transgenic mice. J Clin Invest. 1994;93(4):1403-10.
van Vlijmen, B. J., van den Maagdenberg, A. M., Gijbels, M. J., van der Boom, H., HogenEsch, H., Frants, R. R., Hofker, M. H., & Havekes, L. M. (1994). Diet-induced hyperlipoproteinemia and atherosclerosis in apolipoprotein E3-Leiden transgenic mice. The Journal of Clinical Investigation, 93(4), 1403-10.
van Vlijmen BJ, et al. Diet-induced Hyperlipoproteinemia and Atherosclerosis in Apolipoprotein E3-Leiden Transgenic Mice. J Clin Invest. 1994;93(4):1403-10. PubMed PMID: 8163645.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Diet-induced hyperlipoproteinemia and atherosclerosis in apolipoprotein E3-Leiden transgenic mice. AU - van Vlijmen,B J, AU - van den Maagdenberg,A M, AU - Gijbels,M J, AU - van der Boom,H, AU - HogenEsch,H, AU - Frants,R R, AU - Hofker,M H, AU - Havekes,L M, PY - 1994/4/1/pubmed PY - 1994/4/1/medline PY - 1994/4/1/entrez SP - 1403 EP - 10 JF - The Journal of clinical investigation JO - J. Clin. Invest. VL - 93 IS - 4 N2 - Apolipoprotein E3-Leiden (APOE*3-Leiden) transgenic mice have been used to study the effect of different cholesterol-containing diets on the remnant lipoprotein levels and composition and on the possible concurrent development of atherosclerotic plaques. On high fat/cholesterol (HFC) diet, the high expressing lines 2 and 181 developed severe hypercholesterolemia (up to 40 and 60 mmol/liter, respectively), whereas triglyceride levels remained almost normal when compared with regular mouse diet. The addition of cholate increased the hypercholesterolemic effect of this diet. In lines 2 and 181, serum levels of apo E3-Leiden also increased dramatically upon cholesterol feeding (up to 107 and 300 mg/dl, respectively). In these high expressing APOE*3-Leiden transgenic mice, the increase in both serum cholesterol and apo E3-Leiden occurred mainly in the VLDL/LDL-sized fractions, whereas a considerable increase in large, apo E-rich HDL particles also occurred. In contrast to the high expressing lines, the low expressing line 195 reacted only mildly upon HFC diet. On HFC diets, the high expresser APOE*3-Leiden mice developed atherosclerotic lesions in the aortic arch, the descending aorta, and the carotid arteries, varying from fatty streaks containing foam cells to severe atherosclerotic plaques containing cholesterol crystals, fibrosis, and necrotic calcified tissue. Quantitative evaluation revealed that the atherogenesis is positively correlated with the serum level of cholesterol-rich VLDL/LDL particles. In conclusion, with APOE*3-Leiden transgenic mice, factors can be studied that influence the metabolism of remnant VLDL and the development of atherosclerosis. SN - 0021-9738 UR - https://www.unboundmedicine.com/medline/citation/8163645/Diet_induced_hyperlipoproteinemia_and_atherosclerosis_in_apolipoprotein_E3_Leiden_transgenic_mice_ L2 - https://doi.org/10.1172/JCI117117 DB - PRIME DP - Unbound Medicine ER -