Oral amphipathic peptides as therapeutic agents.

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.

• Authors: Srinivasa T Reddy, G M Anantharamaiah, Mohamad Navab, Susan Hama, Gregory Hough, Victor Grijalva, David W Garber, Geeta Datta, Alan M Fogelman
• Journal: Expert opinion on investigational drugs (Expert Opin Investig Drugs) Vol. 15 Issue 1 Pg. 13-21 (Jan 2006) ISSN: 1744-7658 [Electronic] England
• PMID: 16370930 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Anti-Inflammatory Agents
• Apolipoprotein A-I
• Clusterin
• D-4F peptide
• Lipoproteins, HDL
• Peptides
• Cholesterol

Topics

• Administration, Oral
• Animals
• Anti-Inflammatory Agents (administration & dosage, chemistry, therapeutic use)
• Apolipoprotein A-I (chemistry)
• Atherosclerosis (drug therapy, immunology, metabolism)
• Cholesterol (immunology, metabolism)
• Clusterin (chemistry)
• Disease Models, Animal
• Drug Evaluation, Preclinical
• Endothelial Cells (metabolism)
• Humans
• Immunity, Innate
• Inflammation (immunology, metabolism)
• Lipoproteins, HDL (immunology, metabolism)
• Molecular Mimicry
• Peptides (administration & dosage, chemistry, therapeutic use)
• Protein Structure, Secondary