Diet-induced atherosclerosis in mice heterozygous and homozygous for apolipoprotein E gene disruption. (original) (raw)
Research Article Free access | 10.1172/JCI117460
Department of Pathology, School of Medicine, University of North Carolina at Chapel Hill 27599-7525.
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Department of Pathology, School of Medicine, University of North Carolina at Chapel Hill 27599-7525.
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Department of Pathology, School of Medicine, University of North Carolina at Chapel Hill 27599-7525.
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Department of Pathology, School of Medicine, University of North Carolina at Chapel Hill 27599-7525.
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Published September 1, 1994 -More info
Published September 1, 1994 -Version history
With the aim of establishing whether a genetically reduced capability of producing apolipoprotein E (apo E) can affect atherogenesis, we have compared the consequences of dietary stress on normal mice and on mice heterozygous or homozygous for a disrupted apo E gene. A dramatically accelerated development of lesions occurred in the vasculature of the homozygous mutants as a result of feeding an atherogenic diet for 12 wk, and extensive deposition of lipid-filled macrophages was found outside the cardiovascular system. In nine heterozygotes fed the atherogenic diet for 12 wk, the amount of apo E in their total plasma lipoproteins increased to a level comparable to normal, but all nine developed much larger foam cell lesions in their proximal aorta than those found in 3 of 9 normal mice fed the same diet. The other six normals had no lesions. Our study demonstrates that heterozygous mice with only one functional apo E gene are more susceptible to diet-induced atherosclerosis than are normal, two-copy mice. Genetically determined quantitative limitations of apo E could, therefore, have similar effects in humans when they are stressed by an atherogenic diet.
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