Membrane microdomains modulate oligomeric ABCA1 function: impact on apoAI-mediated lipid removal and phosphatidylcholine biosynthesis.

Recent studies have identified an ABCA1-dependent, phosphatidylcholine-rich microdomain, called the "high-capacity binding site" (HCBS), that binds apoA-I and plays a pivotal role in apoA-I lipidation. Here, using sucrose gradient fractionation, we obtained evidence that both ABCA1 and [¹²⁵I]apoA-I associated with the HCBS were found localized to nonraft microdomains. Interestingly, phosphatidylcholine (PtdCho) was selectively removed from nonraft domains by apoA-I, whereas sphingomyelin and cholesterol were desorbed from both detergent-resistant membranes and nonraft domains.

The HDL proteome in acute coronary syndromes shifts to an inflammatory profile.

Inflammation is a major factor underlying acute coronary syndromes (ACS). HDL particles may be remodeled, becoming functionally defective, under the inflammatory conditions seen in ACS. Shotgun proteomics was used to monitor changes in the HDL proteome between male age-matched control, stable CAD, and ACS subjects (n=10/group).

RVX-208: a small molecule that increases apolipoprotein A-I and high-density lipoprotein cholesterol in vitro and in vivo.

Objectives: The aim of this study was to determine whether a novel small molecule RVX-208 affects apolipoprotein (apo)A-I and high-density lipoprotein cholesterol (HDL-C) levels in vitro and in vivo.

Background: Increased apoA-I and HDL-C levels are potential therapeutic targets for reducing atherosclerotic disease.

Methods: HepG2 cells were treated with 0 to 60 mumol/l RVX-208 followed by assays for apoA-I and HDL-C production.

Analysis of lipid transfer activity between model nascent HDL particles and plasma lipoproteins: implications for current concepts of nascent HDL maturation and genesis.

The specifics of nascent HDL remodeling within the plasma compartment remain poorly understood. We developed an in vitro assay to monitor the lipid transfer between model nascent HDL (LpA-I) and plasma lipoproteins. Incubation of alpha-(125)I-LpA-I with plasma resulted in association of LpA-I with existing plasma HDL, whereas incubation with TD plasma or LDL resulted in conversion of alpha-(125)I-LpA-I to prebeta-HDL.

Comparison of treatment of severe high-density lipoprotein cholesterol deficiency in men with daily atorvastatin (20 mg) versus fenofibrate (200 mg) versus extended-release niacin (2 g).

To determine whether available lipid-modifying medication can increase high-density lipoprotein (HDL) cholesterol in well-defined genetic or familial HDL-deficiency states, we studied 19 men with HDL deficiency (HDL cholesterol <5th percentile for age and gender) 55 +/- 10 years of age. Concomitant risk factors included diabetes (n = 3) and hypertension (n = 7) and 8 patients had coronary artery disease. Molecular analysis revealed that 4 patients had a mutation in the ABCA1 gene.