The 5A apolipoprotein A-I mimetic peptide displays antiinflammatory and antioxidant properties in vivo and in vitro.

Abstract

OBJECTIVE:

The apolipoprotein (apo)A-I mimetic peptide 5A is highly specific for ATP-binding cassette transporter (ABC)A1-mediated cholesterol efflux. We investigated whether the 5A peptide shares other beneficial features of apoA-I, such as protection against inflammation and oxidation. Methods- New Zealand white rabbits received an infusion of apoA-I, reconstituted high-density lipoprotein (HDL) containing apoA-I ([A-I]rHDL), or the 5A peptide complexed with phospholipids (1-palmitoyl-2-linoleoyl phosphatidylcholine [PLPC]), before inserting a collar around the carotid artery. Human coronary artery endothelial cells (HCAECs) were incubated with (A-I)rHDL or 5A/PLPC before stimulation with tumor necrosis factor alpha. Results- ApoA-I, (A-I)rHDL, and 5A/PLPC reduced the collar-mediated increase in (1) endothelial expression of cell adhesion molecules vascular cell adhesion molecule-1 and intercellular adhesion molecule-1; (2) production, as well as the expression of the Nox4 catalytic subunits of the NADPH oxidase; and (3) infiltration of circulating neutrophils into the carotid intima-media. In HCAECs, both 5A/PLPC and (A-I)rHDL inhibited tumor necrosis factor-alpha-induced intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression, as well as the nuclear factor kappaB signaling cascade and production. The effects of the 5A/PLPC complex were no longer apparent in HCAECs knocked down for ABCA1.

CONCLUSIONS:

Like apoA-I, the 5A peptide inhibits acute inflammation and oxidative stress in rabbit carotids and HCAECs. In vitro, the 5A peptide exerts these beneficial effects through interaction with ABCA1.

• Authors: Fatiha Tabet, Alan T Remaley, Aude I Segaliny, Jonathan Millet, Ling Yan, Shirley Nakhla, Philip J Barter, Kerry-Anne Rye, Gilles Lambert
• Journal: Arteriosclerosis, thrombosis, and vascular biology (Arterioscler Thromb Vasc Biol) Vol. 30 Issue 2 Pg. 246-52 (Feb 2010) ISSN: 1524-4636 [Electronic] United States
• PMID: 19965776 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ABCA1 protein, human
• ATP Binding Cassette Transporter 1
• ATP-Binding Cassette Transporters
• Anti-Inflammatory Agents
• Antioxidants
• Apolipoprotein A-I
• Lipoproteins, HDL
• NF-kappa B
• Peptides
• Phosphatidylcholines
• RNA, Messenger
• Recombinant Proteins
• Tumor Necrosis Factor-alpha
• Vascular Cell Adhesion Molecule-1
• Superoxides
• Intercellular Adhesion Molecule-1
• 1-palmitoyl-2-linoleoylphosphatidylcholine
• NADPH Oxidases

Topics

• ATP Binding Cassette Transporter 1
• ATP-Binding Cassette Transporters (genetics, metabolism)
• Adult
• Animals
• Anti-Inflammatory Agents (administration & dosage, metabolism, pharmacology)
• Antioxidants (administration & dosage, metabolism, pharmacology)
• Apolipoprotein A-I (administration & dosage, metabolism, pharmacology)
• Carotid Arteries (drug effects, metabolism, pathology)
• Carotid Artery Diseases (drug therapy, metabolism, pathology)
• Cells, Cultured
• Disease Models, Animal
• Endothelial Cells (drug effects, metabolism)
• Gene Expression Regulation, Enzymologic (drug effects)
• Humans
• Intercellular Adhesion Molecule-1 (metabolism)
• Lipoproteins, HDL (metabolism)
• Male
• Molecular Mimicry
• NADPH Oxidases (genetics, metabolism)
• NF-kappa B (metabolism)
• Neutrophil Infiltration (drug effects)
• Peptides (administration & dosage, metabolism, pharmacology)
• Phosphatidylcholines (metabolism)
• RNA Interference
• RNA, Messenger (metabolism)
• Rabbits
• Recombinant Proteins (metabolism)
• Signal Transduction (drug effects)
• Superoxides (metabolism)
• Time Factors
• Transfection
• Tumor Necrosis Factor-alpha (metabolism)
• Vascular Cell Adhesion Molecule-1 (metabolism)
• Young Adult