OBJECTIVE Preclinical and clinical studies have shown beneficial effects of infusions of apolipoprotein A-I (ApoA-I) on atherosclerosis. ApoA-I is also a target for myeloperoxidase-mediated oxidation, leading in vitro to a loss of its ability to promote ATP-binding cassette transporter A1-dependent macrophage cholesterol efflux. Therefore, we hypothesized that myeloperoxidase-mediated ApoA-I ox...

To test the hypothesis that apolipoprotein A-I (apoA-I) functions specifically to inhibit atherosclerosis independent of the level of high-density lipoprotein cholesterol (HDL-C) by promoting both reverse cholesterol transport and HDL antiinflammatory function in vivo, we established a murine atherosclerosis model of apoA-I deficiency in which the level of HDL-C is well maintained. ApoA-I / mic...

We reported previously that apolipoprotein A-I (apoA-I) is oxidatively modified in the artery wall at tyrosine 166 (Tyr(166)), serving as a preferred site for post-translational modification through nitration. Recent studies, however, question the extent and functional importance of apoA-I Tyr(166) nitration based upon studies of HDL-like particles recovered from atherosclerotic lesions. We dev...

Screening for genes overexpressed in trout aflatoxin B1-induced hepatocellular carcinomas resulted in the isolation of cDNA sequences of two apolipoprotein A-Is, apoA-I-1 and apoA-I-2. The levels of apoA-I-1 and -2 mRNAs of liver and tumor were quite different. ApoA-I-1 mRNA was the major species in liver, while apoA-I-1 and -2 mRNAs were present at similar levels in several tumors. This elevat...

The contribution of ABCA1-mediated efflux of cellular phospholipid (PL) and cholesterol to human apolipoprotein A-I (apoA-I) to the formation of pre beta 1-HDL (or lipid-poor apoA-I) is not well defined. To explore this issue, we characterized the nascent HDL particles formed when lipid-free apoA-I was incubated with fibroblasts in which expression of the ABCA1 was upregulated. After a 2 h incu...

OBJECTIVE The present study is a comparative investigation of cellular lipid mobilization and efflux to lipid-free human apoA-I and apoA-I(Milano), reconstituted high-density lipoprotein (rHDL) particles containing these proteins and serum isolated from mice expressing human apoA-I or apoA-I(Milano). METHODS AND RESULTS Cholesterol and phospholipid efflux to these acceptors was measured in ce...

Estrogen replacement therapies, such as conjugated equine estrogen (CEE, Premarin), reduce the risk of coronary heart disease among postmenopausal women. In the present study, a HepG2 stable cell line (HepG2/S) that harbors a luciferase reporter gene cassette with the human apolipoprotein A-I (apoA-I) promoter region was used to examine the activity of CEE components in modulating human apoA-I ...

the peroxisome proliferator-activated receptors (ppars) -α, -δ/β and -γ are the ligand-activated transcription factors involved in the regulation of fatty acid and lipoprotein metabolism, energy balance, cell proliferation and differentiation and atherosclerosis, etc. we investigated the associations of 10 single-nucleotide polymorphisms (snps) in ppars with apolipoprotein (apo) a-i/apob ratio ...

In vitro phosphorylation of purified human plasma apolipoprotein A-I (apoA-I) by a recently characterized Ca2+/calmodulin-dependent kinase (Beg, Z. H., Stonik, J. A., and Brewer, H. B., Jr. (1987) J. Biol. Chem. 262, 13228-13240) was time-, Ca2+-, and calmodulin-dependent. Maximal phosphorylation of human apoA-I revealed a stoichiometry of approximately 1 mol of PO4/mol of apoA-I. Phosphorylati...