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Research Article Free access | 10.1172/JCI119479

Paradoxical enhancement of atherosclerosis by probucol treatment in apolipoprotein E-deficient mice.

S H Zhang, R L Reddick, E Avdievich, L K Surles, R G Jones, J B Reynolds, S H Quarfordt, and N Maeda

Department of Pathology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7525, USA.

Find articles by Zhang, S. in: PubMed | Google Scholar

Department of Pathology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7525, USA.

Find articles by Reddick, R. in: PubMed | Google Scholar

Department of Pathology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7525, USA.

Find articles by Avdievich, E. in: PubMed | Google Scholar

Department of Pathology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7525, USA.

Find articles by Surles, L. in: PubMed | Google Scholar

Department of Pathology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7525, USA.

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Department of Pathology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7525, USA.

Find articles by Reynolds, J. in: PubMed | Google Scholar

Department of Pathology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7525, USA.

Find articles by Quarfordt, S. in: PubMed | Google Scholar

Department of Pathology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7525, USA.

Find articles by Maeda, N. in: PubMed | Google Scholar

Published June 15, 1997 - More info

Published in Volume 99, Issue 12 on June 15, 1997
J Clin Invest. 1997;99(12):2858–2866. https://doi.org/10.1172/JCI119479.
© 1997 The American Society for Clinical Investigation
Published June 15, 1997 - Version history
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Abstract

Dietary administration of probucol (0.5%, wt/wt) efficiently reduced total plasma cholesterol levels in apolipoprotein E-deficient mice (apoE-/-) by 40%, with decreases in high density lipoprotein (HDL) and apoAI by 70 and 50%, respectively. Paradoxically, however, aortic atherosclerotic plaques in the probucol-treated apoE-/- mice formed more rapidly than in the untreated apoE-/- mice, and the lesions were two to four times larger and more mature regardless of sex, age, and genetic background (P < 10(-)6). Histologically, lesions in probucol-treated mice contained increased fibrous materials and cells other than foam cells, and were commonly associated with focal inflammation and aneurysmal dilatation. Probucol treatment also accelerated lesion development in apoE+/- mice fed an atherogenic diet, indicating that the adverse effect is not dependent on the complete absence of apoE. Furthermore, mice lacking apoE and apoAI have plasma lipoprotein profiles very similar to the probucol-treated apoE-/- mice, but do not have accelerated plaque development. Thus, the enhanced atherosclerosis in the probucol-treated animals is unlikely to be caused by the reduction of HDL and apoAI levels. Our data indicate that a reduction in plasma cholesterol caused by probucol does not necessarily lead to an antiatherogenic effect.

Version history
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