Intestine may be a major site of action for the apoA-I mimetic peptide 4F whether administered subcutaneously or orally.

Academic Article

Abstract

  • To determine if the dose of peptide administered or the plasma level was more important, doses of 0.15, 0.45, 4.5, or 45 mg/kg/day of the peptide D-4F were administered orally or subcutaneously (SQ) to apoliptotein (apo)E null mice. Plasma levels of peptide were ∼1,000-fold higher when administered SQ compared with orally. Regardless of the route of administration, doses of 4.5 and 45 mg/kg significantly reduced plasma serum amyloid A (SAA) levels and the HDL inflammatory index (P < 0.0001); doses of 0.15 or 0.45 mg/kg did not. A dose of 45 mg/kg/day administered to apoE null mice on a Western diet reduced aortic atherosclerosis by ∼50% (P < 0.0009) whether administered orally or SQ and also significantly reduced plasma levels of SAA (P < 0.002) and lysophosphatidic acid (P < 0.0009). Remarkably, for each dose administered, the concentration and amount of peptide in the feces was similar regardless of whether the peptide was administered orally or SQ. We conclude: i) the dose of 4F administered and not the plasma level achieved determines efficacy; ii) the intestine may be a major site of action for the peptide regardless of the route of administration.
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    Keywords

  • Administration, Cutaneous, Administration, Oral, Amino Acid Sequence, Animals, Apolipoprotein A-I, Apolipoproteins E, Atherosclerosis, Diet, Disease Models, Animal, Dose-Response Relationship, Drug, Feces, Female, Gene Deletion, Inflammation, Intestinal Mucosa, Lipoproteins, HDL, Liver, Lysophospholipids, Mice, Mice, Knockout, Molecular Mimicry, Molecular Sequence Data, Peptides, Serum Amyloid A Protein
  • Digital Object Identifier (doi)

    Authorlist

  • Navab M; Reddy ST; Anantharamaiah GM; Imaizumi S; Hough G; Hama S; Fogelman AM
  • Start Page

  • 1200
  • End Page

  • 1210
  • Volume

  • 52
  • Issue

  • 6