Oral administration of an Apo A-I mimetic Peptide synthesized from D-amino acids dramatically reduces atherosclerosis in mice independent of plasma cholesterol.
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.
Navab
Mohamad
M
Department of Medicine, University of California Los Angeles, California, USA. mnavab@mednet.ucla.edu
Anantharamaiah
G M
GM
Hama
Susan
S
Garber
David W
DW
Chaddha
Manjula
M
Hough
Greg
G
Lallone
Roger
R
Fogelman
Alan M
AM
D000284:Administration, Oral; D000596:Amino Acids / Q000096:biosynthesis; D000818:Animals; D016632:Apolipoprotein A-I / Q000008:administration & dosage / Q000138:chemical synthesis / Q000627:therapeutic use*; D001057:Apolipoproteins E / Q000235:genetics; D001161:Arteriosclerosis / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D002478:Cells, Cultured; D002633:Chemotaxis; D002784:Cholesterol / Q000097:blood*; D018920:Coculture Techniques; D005260:Female; D008075:Lipoproteins, HDL / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D010455:Peptides / Q000008:administration & dosage / Q000138:chemical synthesis / Q000627:therapeutic use; D011973:Receptors, LDL / Q000235:genetics
D000596:Amino Acids; D016632:Apolipoprotein A-I; D001057:Apolipoproteins E; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D010455:Peptides; D011973:Receptors, LDL; C099252:oxidized low density lipoprotein; D002784:Cholesterol