Diet-induced hyperlipoproteinemia and atherosclerosis in apolipoprotein E3-Leiden transgenic mice

Bart J M Van Vlijmen, Arn M J M Van Den Maagdenberg, Marion J J Gijbels, Hans Van Der Boom, Harm HogenEsch, Rune R. Frants, Marten H. Hofker, Louis M. Havekes

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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.

Original languageEnglish (US)
Pages (from-to)1403-1410
Number of pages8
JournalJournal of Clinical Investigation
Volume93
Issue number4
StatePublished - Apr 1994
Externally publishedYes

Fingerprint

Apolipoprotein E3
Hyperlipoproteinemias
Transgenic Mice
Atherosclerosis
Cholesterol
Diet
High Fat Diet
Thoracic Aorta
Atherosclerotic Plaques
Serum
Cholates
VLDL Cholesterol
Foam Cells
Apolipoproteins E
Hypercholesterolemia
Carotid Arteries
Lipoproteins
Triglycerides
Fibrosis

Keywords

  • atherosclerotic plaques
  • cholesterol- rich diets
  • familial dysbetalipoproteinemia
  • hypercholesterolemia
  • hypertriglyceridemia

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Van Vlijmen, B. J. M., Van Den Maagdenberg, A. M. J. M., Gijbels, M. J. J., Van Der Boom, H., HogenEsch, H., Frants, R. R., ... Havekes, L. M. (1994). Diet-induced hyperlipoproteinemia and atherosclerosis in apolipoprotein E3-Leiden transgenic mice. Journal of Clinical Investigation, 93(4), 1403-1410.

Diet-induced hyperlipoproteinemia and atherosclerosis in apolipoprotein E3-Leiden transgenic mice. / Van Vlijmen, Bart J M; Van Den Maagdenberg, Arn M J M; Gijbels, Marion J J; Van Der Boom, Hans; HogenEsch, Harm; Frants, Rune R.; Hofker, Marten H.; Havekes, Louis M.

In: Journal of Clinical Investigation, Vol. 93, No. 4, 04.1994, p. 1403-1410.

Research output: Contribution to journalArticle

Van Vlijmen, BJM, Van Den Maagdenberg, AMJM, Gijbels, MJJ, Van Der Boom, H, HogenEsch, H, Frants, RR, Hofker, MH & Havekes, LM 1994, 'Diet-induced hyperlipoproteinemia and atherosclerosis in apolipoprotein E3-Leiden transgenic mice', Journal of Clinical Investigation, vol. 93, no. 4, pp. 1403-1410.
Van Vlijmen BJM, Van Den Maagdenberg AMJM, Gijbels MJJ, Van Der Boom H, HogenEsch H, Frants RR et al. Diet-induced hyperlipoproteinemia and atherosclerosis in apolipoprotein E3-Leiden transgenic mice. Journal of Clinical Investigation. 1994 Apr;93(4):1403-1410.
Van Vlijmen, Bart J M ; Van Den Maagdenberg, Arn M J M ; Gijbels, Marion J J ; Van Der Boom, Hans ; HogenEsch, Harm ; Frants, Rune R. ; Hofker, Marten H. ; Havekes, Louis M. / Diet-induced hyperlipoproteinemia and atherosclerosis in apolipoprotein E3-Leiden transgenic mice. In: Journal of Clinical Investigation. 1994 ; Vol. 93, No. 4. pp. 1403-1410.
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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.",
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AU - Van Der Boom, Hans

AU - HogenEsch, Harm

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