Abstract 12493: FAMP, A Powerful Producer of Pre-Beta HDL via an ABCA1-Mediated Cholesterol Efflux Pathway
Apolipoprotein (apo) stimulates cholesterol efflux via the ATP-binding cassette transporter A1 (ABCA1), thus generating HDL and reversing the macrophage foam-cell phenotype. Despite these anti-atherogenic roles, the impact of specifically promoting ABCA1 cholesterol efflux on the development of atherosclerosis is not well known. In this report, we describe FAMP, a novel apoA-I mimetic peptide of 24 amino acids without phospholipids. In cholesterol efflux, lipid-free apoA-I from human plasma and FAMP could take up cholesterol from A172 cells. Interestingly, after stimulation with T0901317 and 9-cis-retinoic acid, both plasma apoA-I and FAMP-mediated cholesterol efflux were drastically increased in A172 cells (apoA-I, 2.60-fold increase; FAMP, 3.26-fold increase, p<0.01, respectively). Furthermore, FAMP stimulated cholesterol efflux by the ABCA1 transporter with a higher specificity (ABCA1-transfected versus mock-transfected cells; 1.46±0.08% versus 2.98±0.18%, p<0.01). After human normolipidemic plasma was incubated with FAMP, a lipid profile was measured by agarose gel electrophoresis and capillary isotachophoresis. Ten minutes after incubation with FAMP at 37°C, the subfraction of pre-beta HDL increased. Finally, 10 days of i.p. infusion of FAMP in C57BL6 mice by an osmotic pump Resultsed in an increase in HDL-C from 38.9±9.3 to 57.8±2.6 mg/dl. In summary, FAMP markedly increases pre-beta HDL, as well as overall cholesterol efflux from peripheral tissues, particularly from macrophages, and this depends on ABCA1.
- © 2010 by American Heart Association, Inc.