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

van Vlijmen BJ
TNO Institute of Ageing and Vascular Research, Gaubius Laboratory, Leiden, The Netherlands.
van den Maagdenberg AM
No affiliation info available
Gijbels MJ
No affiliation info available
van der Boom H
No affiliation info available
HogenEsch H
No affiliation info available
Frants RR
No affiliation info available
Hofker MH
No affiliation info available
Havekes LM
No affiliation info available

MeSH

AnimalsApolipoprotein E3Apolipoproteins EArteriosclerosisCholesterol, DietaryFemaleHyperlipoproteinemiasLipidsMaleMiceMice, Inbred C57BLMice, Inbred CBAMice, TransgenicSex Factors

Pub Type(s)

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

Language

eng

PubMed ID

8163645