In vivo biological activity of a ApoA-I mimetic peptide.

Apolipoprotein A-I (ApoA-I), the major protein component of HDL, plays a key role in reverse cholesterol transport, mainly by stimulating the efflux of cholesterol and activating the enzyme LCAT. LCAT converts cholesterol into cholesteryl esters and addresses them to HDL for transport into the circulation. The binding of haptoglobin (Hpt) to ApoA-I is associated with inhibition of LCAT activity[1]. On the basis of the above information, high levels of Hpt, as occurring during the acute phase of inflammation[2], were suggested to be a major cause of both poor cholesterol removal from peripheral cells and low level of HDL cholesterol in the circulation. Previously, we showed that an ApoA-I mimetic peptide (P2a), with amino acid sequence overlapping the stimulatory site for LCAT, was effective in displacing Hpt from ApoA-I, and able to rescue in vitro the stimulatory function of ApoA-I in the presence of high Hpt levels[3]. In this work we characterized the biological activity of peptide P2a in an experimental model of inflammation. In particular, we verified the ability of peptide P2a to rescue LCAT dependent cholesterol esterification in vivo in presence of high level of Hpt. References 1. Balestrieri, M., Cigliano, L., De Simone, M.L., Dale, B., Abrescia, P. Mol. Reprod. Dev. 59, 186 (2001) 2. Langlois MR & Delanghe JR (1996) Biological and clinical significance of haptoglobin polymorphism in humans. Clin Chem 42,1589-1600. 3. Spagnuolo, M.S., Cigliano, L., D’Andrea, L.D., Pedone, C. and Abrescia, P. (2005) Assignment of the binding site for Haptoglobin on Apolipoprotein A-I. J. Biol. Chem. 280, 1193-1198.