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Correspondence to:
Mohamad Navab
Apolipoprotein A-I (apoA-I) and an apoA-I peptide mimetic removed seeding molecules from human low density lipoprotein (LDL) and rendered the LDL resistant to oxidation by human artery wall cells. The apoA-I-associated seeding molecules included hydroperoxyoctadecadienoic acid (HPODE) and hydroperoxyeicosatetraenoic acid (HPETE). LDL from mice genetically susceptible to fatty streak lesion formation was highly susceptible to oxidation by artery wall cells and was rendered resistant to oxidation after incubation with apoA-I in vitro. Injection of apoA-I (but not apoA-II or murine serum albumin) into mice rendered their LDL resistant to oxidation within 3 h. Infusion of apoA-I into humans rendered their LDL resistant to oxidation within 6 h.
We conclude that 1) oxidation of LDL by artery wall cells requires seeding molecules that include HPODE and HPETE; 2) LDL from mice genetically susceptible to atherogenesis is more readily oxidized by artery wall cells; and 3) normal HDL and its components can remove or inhibit the activity of lipids in freshly isolated LDL that are required for oxidation by human artery wall cells.Navab, M., S. Y. Hama, C. J. Cooke, G. M. Anantharamaiah, M. Chaddha, L. Jin, G. Subbanagounder, K. F. Faull, S. T. Reddy, N. E. Miller, and A. M. Fogelman. Normal high density lipoprotein inhibits three steps in the formation of mildly oxidized low density lipoprotein: step 1. J. Lipid Res. 2000. 41: 1481;1494.
Supplementary key words:
LDL, HDL, mildly oxidized LDL, MM-LDL, oxidized phospholipids, HPODE, HPETE, cholesteryl linoleate hydroperoxide, paraoxonase, atherosclerosis, antioxidant
Copyright © 2000 by Lipid Research, Inc.
Original Article
Normal high density lipoprotein inhibits three steps in the formation of mildly oxidized low density lipoprotein: step 1
Mohamad Navaba,
Susan Y. Hamaa,
C. Justin Cookeb,
G. M. Anantharamaiahc,
Manjula Chaddhac,
Linda Jina,
Ganesamoorthy Subbanagoundera,
Kym F. Faulld,
Srinivasa T. Reddya,
Norman E. Millerb, and
Alan M. Fogelmana
a Atherosclerosis Research Unit, Division of Cardiology, Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095
b St. Bartholomew's and the Royal London School of Medicine and Dentistry, London, UK EC1M 6BQ
c Department of Medicine and the Atherosclerosis Research Unit, University of Alabama, Birmingham, AL 35294
d Neuropsychiatric Institute, University of California, Los Angeles, Los Angeles, CA 90095
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