Potential clinical utility of high-density lipoprotein-mimetic peptides.

Academic Article

Abstract

  • PURPOSE OF REVIEW: To determine the potential clinical utility of high-density lipoprotein-mimetic peptides. RECENT FINDINGS: Oral administration of D-4F together with pravastatin caused lesion regression in old apoE null mice. Administration of D-4F to low-density lipoprotein receptor null mice fed a Western diet reduced the association of myeloperoxidase with apoA-I and reduced the 3-nitrotyrosine content of apoA-I. Oral D-4F improved arterial vasoreactivity independent of apoA-I. Mice genetically lacking apoA-I showed significant improvement in vasoreactivity but, in contrast to mice with apoA-I, did not demonstrate reduced arterial wall thickness after D-4F treatment. In a rat model of diabetes, D-4F administration induced heme oxygenase-1 and extracellular superoxide dismutase, prevented endothelial sloughing, and dramatically improved arterial vasoreactivity. A peptide with 10 D-amino acid residues taken from the sequence of apoJ rendered high-density lipoprotein anti-inflammatory in mice and monkeys, and dramatically reduced atherosclerosis in apoE null mice. Oral administration of tetrapeptides synthesized from either L-amino acids or D-amino acids rendered high-density lipoprotein anti-inflammatory in mice and monkeys, and reduced atherosclerosis in apoE null mice. SUMMARY: Peptides that sequester lipoprotein lipid hydroperoxides release a series of high-density lipoprotein-associated antioxidant enzymes such as paraoxonase from inhibition and protect apoA-I from oxidative damage that would impair cholesterol efflux.
  • Published In

    Keywords

  • Animals, Anti-Inflammatory Agents, Apolipoproteins, Atherosclerosis, Biomimetic Materials, Lipoproteins, HDL, Peptides
  • Digital Object Identifier (doi)

    Pubmed Id

  • 20166817
  • Author List

  • Navab M; Anantharamaiah GM; Reddy ST; Van Lenten BJ; Datta G; Garber D; Fogelman AM
  • Start Page

  • 440
  • End Page

  • 444
  • Volume

  • 17
  • Issue

  • 4