An apolipoprotein A-I mimetic dose-dependently increases the formation of preβ1 HDL in human plasma

Abstract

Preb 1 HDL is the initial plasma acceptor of cellderived cholesterol in reverse cholesterol transport. Recently, small amphipathic peptides composed of D-amino acids have been shown to mimic apolipoprotein A-I (apoA-I) as a precursor for HDL formation. ApoA-I mimetic peptides have been proposed to stimulate the formation of preb 1 HDL and increase reverse cholesterol transport in apoE-null mice. The existence of a monoclonal antibody (MAb 55201) and a corresponding ELISA method that is selective for the detection of the preb 1 subclass of HDL provides a means of establishing a correlation between apoA-I mimetic dose and preb 1 HDL formation in human plasma. Using this preb 1 HDL ELISA, we demonstrate marked apoA-I mimetic dosedependent preb 1 HDL formation in human plasma. These results correlated with increases in band density of the plasma preb 1 HDL, when observed by Western blotting, as a function of increased apoA-I mimetic concentration. Increased preb 1 HDL formation was observed after as little as 1 min and was maximal within 1 h. Together, these data suggest that a high-throughput preb 1 HDL ELISA provides a way to quantitatively measure a key component of the reverse cholesterol transport pathway in human plasma, thus providing a possible method for the identification of apoA-I mimetic molecules.-Troutt, J.

Enhancement by LDL of transfer of L-4F and oxidized lipids to HDL in C57BL/6J mice and human plasma

“…First, it has been shown that 4F can cause the remodeling of HDL and the formation of pre ␤ HDL enriched in both apoA-I and paraoxonase activity ( 29,30 ). This transformation lowers lipoprotein hydroperoxide levels; HDL becomes anti-infl ammatory; and HDL-mediated cholesterol effl ux and reverse cholesterol transport from macrophages are stimulated ( 29 ).…”

Evidence for the presence of lipid-free monomolecular apolipoprotein A-1 in plasma

“…We previously obtained a monoclonal antibody (MAb) 55201 (MAb55201) that specifically recognizes apoA-1 in pre ␤ 1-HDL and developed an ELISA for easily measuring plasma pre ␤ 1-HDL concentrations using the MAb ( 21 ). Recently a variety of research results on pre ␤ 1-HDL using the ELISA were reported, in particular the relationships between plasma pre ␤ 1-HDL concentrations and coronary artery disease and medications have been noted (22)(23)(24)(25)(26).…”

D4F alleviates macrophage-derived foam cell apoptosis by inhibiting CD36 expression and ER stress-CHOP pathway

“…Several lines of evidence demonstrate that D4F exhibits an anti-atherogenic effect without changing plasma cholesterol levels in dyslipidemic mouse models (17)(18)(19)(20). It has been reported that D4F can increase paraoxonase activity in HDL, induce pre-␤ HDL formation, improve HDL-mediated reverse cholesterol transport and antiinfl ammatory properties, and promote endothelial progenitor cell proliferation, migration, and adhesion, which are responsible for its anti-atherogenic role (21)(22)(23). In addition, our recent work has shown that D4F is able to inhibit ox-LDL-induced cytotoxicity on human umbilical vein endothelial cells via preventing the downregulation of pigment epithelium-derived factor ( 24 ), consistent with the report that small dense HDL3 potently protects endothelial cells from ox-LDL-induced apoptosis and that apoA-I is pivotal to such protection ( 25 ).…”