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Results reveal a two-step mechanism for the formation of the major high-density lipoprotein, apolipoprotein A-1, in human vascular cells that involves sequential contributions of the ABC-1 transporter and caveolae. Data indicate that ABC-1-dependent phospholipid efflux precedes free cholesterol efflux to apolipoprotein A-1.

Research has been conducted on the human caveolin gene transcription. The coordination of the growth- and free cholesterol-dependent caveolin expression has been investigated.

Normal human skin fibroblasts synchronized with aphidicolin were used in studying the relationship between mitosis, regulation of cellular free cholesterol transport and the expression of caveolin. FC is a major lipid component of plasma membranes of mammalian cells. Its homeostasis was measured at intervals during the next cell cycle after its inhibitor has been removed. Results indicate that the expression of caveolin influences FC efflux and could possibly be used in measuring FC content and mitosis in skin fibroblasts.

The kinetics of transport of low-density lipoprotein (LDL)-derived 3H-free cholesterol (FC) within the cell wall were investigated by density-gradient ultracentrifugal fractionation and in terms of the effects of inhibitors of endocytosis and intracellular transport. Results were in agreement with a role for the trans-Golgi network as an intermediate compartment in the intracellular FC transport.

Plasma membrane caveolae is directly involved in the efflux of both nascent and low density lipoprotein-derived free cholesterol (FC). This transmembrane transport of FC occurs from cultured fibroblasts to the plasma and high density lipoprotein. The cholesterol-rich caveolar fraction increases with an increase in the cellular FC, as evidenced by the transfer of tritium-labeled FC into the cell. Inhibition of caveolar activity leads to a decrease in FC release from the cell.

A study was conducted to determine the mechanism and specificity of the influx of free cholesterol (FC) from plasma and plasma lipoproteins into cultured skin fibroblasts. The results indicate that a high-capacity, ATPase-dependent pathway is responsible for the transport of low-density lipoprotein (LDL) FC into a temporary storage domain in the cell. From there, LDL FC is either transported further into the cell for metabolism or storage, or lost by efflux as high-density lipoprotein is taken in by the cell.

Anti-apolipoprotein A-I (apo A-I) residues 137-144 present in the adjacent structural site of pre-beta-1 high-density lipoprotein increase cellular cholesterol efflux from cell membranes to the plasma. Incorporation of apo A-I antibody raised monoclonally inhibits cholesterol transport. Apo A-I encodes a 22 amino acid repeat sequence with amphipatic alpha-helical structures.

The mechanisms of cholesterol efflux from cultured fibroblasts were reported. It was shown that two distinct pathways contribute to total efflux of cellular cholesterol and phospholipid: one nonspecific or prebeta-high-density lipoprotein (HDL)-independent, and the other dependent on the concentration of prebeta-1-HDL and and on the integrity of a cell-surface protein.

The identification of apolipoprotein A1 (apo A1) as C-terminal procollagen endoproteinase/bone morphogenetic protein-1 (BMP-1) and its role in the maturation of [prebeta.sub.1]-high-density lipoprotein (HDL) are described. It is shown that BMP-1-mediated cleavage of proapo A1 might play a vital role in HDL processing under both physiological and pathophysiological conditions.

The relationship between Platelet-derived growth factor (PGDF), PKC, caveolin-1 and FC effux was explored. The data obtained provided a new evidence for interdependent roles for caveolin in signaling and free cholesterol (FC) homeostasis, identified intermediates of signal transduction leading to FC effux from caveolae and indicated that the level of FC associated with caveolin-1 was a component of cell FC responsive to both platelet-derived growth factor receptor (PDGFR) and protein kinase C (PKC). The study also suggested that Serine-80 played a major role in determining the level of sterol bound to caveolin-1.

Transcriptional regulation of the ATP-binding cassette transporter (ABCA1) gene is complex. It needs the binding of several different transcription factors to the ABCA1 promoter region and multiple transcription start sites.