Oral amphipathic peptides as therapeutic agents.

Academic Article

Abstract

  • Cholesterol can promote inflammation by its ability to stimulate the production of reactive oxygen species that result in the formation of pro-inflammatory oxidised phospholipids. High-density lipoproteins (HDLs) are part of the innate immune response and can be either pro- or anti-inflammatory independently of plasma HDL-cholesterol levels. During systemic inflammation as occurs with atherosclerosis, Apolipoprotein A-I can be altered, reducing its ability to promote reverse cholesterol transport and HDL can become pro-inflammatory. Amphipathic peptides with either a class A amphipathic helix (D-4F) or a class G* amphipathic helix (D-[113-122]apoJ), or even those that are too small to form a helix (KRES and FREL) have some similar characteristics. Their interaction with lipids leads to a reduction in lipoprotein-lipid hydroperoxides that releases HDL-associated antioxidant enzymes, such as paraoxonase, therefore providing antiatherosclerosis and anti-inflammatory activity. In addition, the peptide D-4F stimulates the formation and cycling of pre-beta HDL. These amphipathic peptides appear to have therapeutic potential as oral agents.
  • Keywords

  • Administration, Oral, Animals, Anti-Inflammatory Agents, Apolipoprotein A-I, Atherosclerosis, Cholesterol, Clusterin, Disease Models, Animal, Drug Evaluation, Preclinical, Endothelial Cells, Humans, Immunity, Innate, Inflammation, Lipoproteins, HDL, Molecular Mimicry, Peptides, Protein Structure, Secondary
  • Digital Object Identifier (doi)

    Authorlist

  • Reddy ST; Anantharamaiah GM; Navab M; Hama S; Hough G; Grijalva V; Garber DW; Datta G; Fogelman AM
  • Start Page

  • 13
  • End Page

  • 21
  • Volume

  • 15
  • Issue

  • 1