Abstract
BackgroundThe risk of cardiovascular disease is inversely correlated to level of plasma HDL-c. Moreover, reverse cholesterol transport (RCT) from peripheral tissues to the liver is the most widely accepted mechanism linked to the anti-atherosclerotic activity of HDL. The apolipoprotein A-I (apoA-I) and the ABC transporters play a key role in this process.Adipose tissue constitutes the body's largest pool of free cholesterol. The adipose cell could therefore be regarded as a key factor in cholesterol homeostasis. The present study investigates the capacity of primary cultures of mature human adipocytes to release cholesterol and explores the relationships between apoA-I, ABCA1, and apoE as well as the signaling pathways that could be potentially involved.ResultsWe demonstrate that apoA-I induces a strong increase in cholesterol release and apoE secretion from adipocytes, whereas it has no transcriptional effect on ABCA1 or apoE genes. Furthermore, brefeldin A (BFA), an intracellular trafficking inhibitor, reduces basal cholesterol and apoE secretion, but does not modify induction by apoA-I. The use of statins also demonstrates that apoA-I stimulated cholesterol release is independent of HMG-CoA reductase activation.ConclusionOur work highlights the fact that adipose tissue, and particularly adipocytes, may largely contribute to RCT via a mechanism specifically regulated within these cells. This further supports the argument that adipose tissue must be regarded as a major factor in the development of cardiovascular diseases, in particular atherosclerosis.
Highlights
The risk of cardiovascular disease is inversely correlated to level of plasma high-density lipoprotein cholesterol (HDL-c)
ApoA-I increases cholesterol release in mature human adipocytes It is widely accepted that apolipoprotein A-I (apoA-I) stimulates the efflux of cholesterol in many cellular models
This has been demonstrated in murine adipocyte cell lines such as the 3T3-L1 [18], but to date there are no reports that a study being conducted on primary cultures of human adipocytes
Summary
The risk of cardiovascular disease is inversely correlated to level of plasma HDL-c. reverse cholesterol transport (RCT) from peripheral tissues to the liver is the most widely accepted mechanism linked to the anti-atherosclerotic activity of HDL. Epidemiological studies have repeatedly highlighted a strong inverse correlation between plasma concentrations of high-density lipoprotein cholesterol (HDL-c) and the risk of developing cardiovascular diseases, in particular atherosclerosis, in humans. Reverse cholesterol transport (RCT) from peripheral tissues to the liver is a physiological process that enables the negative regulation of cholesterol deposits via the very low-density and low-density lipoprotein (VLDL and LDL). Poorly lipidated apoA-I and small discoidal shaped particles, preß-HDL, take up cholesterol from peripheral cells. This results in a radical change, giving rise to spherical HDL3 HDL2 particles, due to the fact that particles become enriched in esterified cholesterol (via lecithin cholesterol acyl transferase (LCAT) associated with preß-HDL particles) and phospholipids. The final uptake of HDL2 by the liver involves a selective receptor, the scavenger receptor B1 (SR-B1)
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