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Correspondence to:
Michael R. Hayden
Lipoprotein lipase (LPL) is a key enzyme in lipoprotein metabolism, and has been hypothesized to exert either pro- or anti-atherogenic effects, depending on its localization. Decreased plasma LPL activity is associated with the high triglyceride (TG);–low HDL phenotype that is often observed in patients with premature vascular disease. In contrast, in the vessel wall, decreased LPL may be associated with less lipoprotein retention due to many potential mechanisms and, therefore, decreased foam cell formation. To directly assess this hypothesis, we have distinguished between the effects of variations in plasma and/or vessel wall LPL on atherosclerosis susceptibility in apoE-deficient mice. Reduced LPL in both plasma and vessel wall (LPL+/- E-/-) was associated with increased TG and increased total cholesterol (TC) compared with LPL+/+E-/- sibs. However despite their dyslipidemia, LPL+/-E-/- mice had significantly reduced lesion areas compared to the LPL+/+E-/- mice. Thus, decreased vessel wall LPL was associated with decreased lesion formation even in the presence of reduced plasma LPL activity. In contrast, transgenic mice with increased plasma LPL but with no increase in LPL expression in macrophages, and thus the vessel wall, had decreased TG and TC and significantly decreased lesion areas compared with LPL+/+E-/- mice. This demonstrates that increased plasma LPL activity alone, in the absence of an increase in vessel wall LPL, is associated with reduced susceptibility to atherosclerosis.
Taken together, these results provide in vivo evidence that the contribution of LPL to atherogenesis is significantly influenced by the balance between vessel wall protein (pro-atherogenic) and plasma activity (anti-atherogenic).—Clee, S. M., N. Bissada, F. Miao, L. Miao, A. D. Marais, H. E. Henderson, P. Steures, J. McManus, B. McManus, R. C. LeBoeuf, J. J. P. Kastelein, and M. R. Hayden. Plasma and vessel wall lipoprotein lipase have different roles in atherosclerosis. J. Lipid Res. 2000. 41: 521;–531.
Supplementary key words:
apoE-deficient mice, triglycerides, HDL, lipoprotein retention, C57BL/6
Copyright © 2000 by Lipid Research, Inc.
Original Article
Plasma and vessel wall lipoprotein lipase have different roles in atherosclerosis
Susanne M. Cleea,
Nagat Bissadaa,
Fudan Miaoa,
Li Miaoa,
A. David Maraisb,
Howard E. Hendersonc,
Pieternel Steuresa,
Janet McManusd,
Bruce McManusd,
Renee C. LeBoeufe,
John J. P. Kasteleinf, and
Michael R. Haydena
a Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, BC, Canada V5Z 4H4
b Department of Internal Medicine, University of Cape Town, Cape Town, 7925 South Africa
c Department of Clinical Pathology, Red Cross Children's Hospital, Cape Town, 7700 South Africa
d Department of Pathology and Laboratory Medicine, St. Paul's Hospital-University of British Columbia, Vancouver, Canada V6Z 1Y6
e Department of Pathobiology, University of Washington, Seattle, WA 98195
f Department of Vascular Medicine, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands 1105 AZ
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