The apolipoprotein (apo) A-I mimetic peptide 5A is highly specific for ABCA1-transporter mediated cholesterol efflux. We investigated whether the 5A peptide shares other beneficial features of apoA-I, such as protection against inflammation and oxidation.
New-Zealand White rabbits received an infusion of apoA-I, reconstituted HDL containing apoA-I ((A-I)rHDL) or the 5A peptide complexed with phospholipids (PLPC), prior to inserting a collar around the carotid artery. Human coronary artery endothelial cells (HCAECs) were incubated with (A-I)rHDL or 5A/PLPC prior to TNFa stimulation.
ApoA-I, (A-I)rHDL and 5A/PLPC reduced the collar mediated increase in (i) endothelial expression of cell adhesion molecules VCAM-1 and ICAM-1, (ii) O2− production as well as the expression of the Nox4 catalytic subunits of the NADPH oxidase, and (iii) infiltration of circulating neutrophils into the carotid intima-media. In HCAECs, both 5A/PLPC and (A-I)rHDL inhibited TNFa induced ICAM-1 and VCAM-1 expression as well as the NF-κB signalling cascade and O2− production. The effects of the 5A/PLPC complex were no longer apparent in HCAECs knocked down for ABCA1.
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.