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Circulation. 2002;105:290-292
doi: 10.1161/hc0302.103711
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(Circulation. 2002;105:290.)
© 2002 American Heart Association, Inc.

Brief Rapid Communications

Oral Administration of an Apo A-I Mimetic Peptide Synthesized From D-Amino Acids Dramatically Reduces Atherosclerosis in Mice Independent of Plasma Cholesterol

Mohamad Navab, PhD; G.M. Anantharamaiah, PhD; Susan Hama, BSc; David W. Garber, PhD; Manjula Chaddha, PhD; Greg Hough, MSc; Roger Lallone, PhD; Alan M. Fogelman, MD

From the Department of Medicine (M.N., S.H., G.H., A.M.F.), University of California Los Angeles, Calif; and the Atherosclerosis Research Unit (G.M.A., D.W.G., M.C., R.L.), University of Alabama at Birmingham.

Correspondence to Mohamad Navab, PhD,47-123 CHS, Box 951679, UCLA School of Medicine, Los Angeles, CA 90095-1679. E-mail mnavab{at}mednet.ucla.edu

When apolipoprotein A-I mimetic peptides synthesized from either D- or L-amino acids were given orally to LDL receptor-null mice, only the peptide synthesized from D-amino acids was stable in the circulation and enhanced the ability of HDL to protect LDL against oxidation. The peptide synthesized from L-amino acids was rapidly degraded and excreted in the urine. When a peptide synthesized from D-amino acids (D-4F) was administered orally to LDL receptor-null mice on a Western diet, lesions decreased by 79%. When added to the drinking water of apoE-null mice, D-4F decreased lesions by approximately 75% at the lowest dose tested (0.05 mg/mL). The marked reduction in lesions occurred independent of changes in total plasma or HDL-cholesterol.


Key Words: atherosclerosis • HDL • apo A-I • LDL oxidation




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