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

Author:

Navab Mohamad1,Anantharamaiah G.M.1,Hama Susan1,Garber David W.1,Chaddha Manjula1,Hough Greg1,Lallone Roger1,Fogelman Alan M.1

Affiliation:

1. 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.

Abstract

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.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Physiology (medical),Cardiology and Cardiovascular Medicine

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