HDL Phospholipid Content and Composition as a Major Factor Determining Cholesterol Efflux Capacity From Fu5AH Cells to Human Serum

Abstract

The relationships of cell cholesterol efflux to HDL phospholipid (PL) content and composition in human serum were analyzed in two groups of subjects selected on the basis of their HDL cholesterol (HDL-C) levels: a norm-HDL group (1.10 mmol/L < HDL-C < 1.50 mmol/L) and a high-HDL group (HDL-C > 1.75 mmol/L). In the high-HDL group, the relative fractional efflux was significantly higher than in the norm-HDL group, and in both groups, fractional efflux was correlated with a number of lipoprotein parameters, the best correlation and the only one that remained significant after multivariate analysis being with HDL phospholipid (HDL-PL). Analysis of the HDL-PL subclasses revealed that HDL in the high-HDL sera was enriched with phosphatidylethanolamine (HDL-PE) and relatively deficient in sphingomyelin (HDL-SM) compared with norm-HDL sera. Moreover, the fractional efflux values in the high-HDL group were negatively correlated with the proportion of HDL-PE (r = -.64, P < .0001) and positively correlated with the proportion of HDL-SM (r = .43, P < .01). Thus, this study provides evidence that HDL-PL concentration can be used to predict the capacity of serum to accept cellular cholesterol. Among the differences described between norm-HDL and high-HDL sera, the variability in PE to SM ratio might reflect changes in serum cholesterol acceptors that modulate the first step of reverse cholesterol transport.

Cellular cholesterol efflux to plasma from moderately hypercholesterolaemic type 1 diabetic patients is enhanced, and is unaffected by simvastatin treatment

“…Cholesterol efflux out of Fu5AH cells via SR-BI is largely dependent on mature HDL, and is correlated positively with HDL cholesterol, HDL phospholipids and plasma apo A-I [33,39,44], whereas lipid-poor acceptors, including pre-β HDL, are important in ABCA1-dependent cholesterol efflux [45]. The relatively higher stimulatory effect of diabetic plasma on cholesterol efflux out of Fu5AH cells, compared to fibroblasts, suggests that plasma from type 1 diabetic patients predominantly enhances SR-BI-mediated efflux.…”

Effect of rosiglitazone on HDL metabolism in subjects with metabolic syndrome and low HDL

“…Fu5AH cells effl ux cholesterol primarily through SR-BI and aqueous diffusion ( 23 ). Increases in both the apoE content and percent phospholipid content of HDL have previously been shown to enhance the ability of HDL to accept cholesterol from cells via SR-BI (38)(39)(40). These changes in HDL composition and functionality would be expected to be antiatherogenic because they would be expected to promote reverse cholesterol transport.…”

Acute systemic inflammation up-regulates secretory sphingomyelinase in vivo : A possible link between inflammatory cytokines and atherogenesis

“…First, inflammation plays an important role in atherogenesis (13)(14)(15)(16)(17), and, given the evidence cited above, ASM-mediated ceramide signaling may be responsible for certain inflammatory responses in the developing lesion, such as smooth muscle cell proliferation (25) and apoptosis of macrophages and smooth muscle cells (26,27). Second, one of the products of the ASM gene-secretory SMase (SSMase; see below)-has been linked directly to extracellular subendothelial lipoprotein aggregation, an event that promotes both retention of lipoproteins in the arterial wall and macrophage foam cell formation (25,(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39).…”