No abstract

Remnant-like lipoprotein particles (RLPs) have been implicated as potentially atherogenic lipoproteins. Endothelial dysfunction is known to be an early event in atherosclerosis and an important contributor to the pathogenesis of coronary artery disease. Moreover, there is considerable evidence linking increased RLP cholesterol levels with endothelial dysfunction, reflected by impaired endothelial vasodilatation and abnormal endothelial secretion Remnant-like lipoprotein particles (RLPs), also known as remnant lipoproteins or remnant-like particles, are derived from VLDLs and chylomicrons, which are the major carriers of plasma triglycerides. The actions of lipoprotein lipase and cholesteryl ester transfer protein on VLDL and chylomicrons produce RLPs with decreased triglyceride and increased cholesteryl ester and apolipoprotein E (apoE). Compared with the nascent triglyceride-rich lipoproteins, RLPs are smaller particles, with a higher density and more cholesteryl ester, which seems to give them more potential atherogenic properties.RLPs have been separated on the basis of their size, density, charge, specific lipid components, or apolipoprotein composition. The analytical "gold standard" for measuring triglyceride-rich lipoproteins and remnants is density gradient ultracentrifugation; however, this technique is laborintensive and involves a 24 h analysis to fractionate the plasma lipoproteins. Moreover, only a few samples can be processed at the same time in each ultracentrifuge. Tsai et al.(1) used NMR spectroscopy to perform numerous postprandial analyses of triglyceride-rich lipoproteins in a large interventional study, and observed that chylomicrons and chylomicron remnants/VLDL fraction measurements obtained by NMR had a high degree of correlation with results produced by ultracentrifugation. NMR is a more rapid procedure and uses substantially less sample volume than traditional ultracentrifugation. And NMR is a physical procedure, so that plasma samples can be preserved for biochemical assays of stable analytes. However, NMR is a relatively expensive method, with a special analyzer, and is not widely available in clinical laboratories at present.Recently, a novel immunoseparation method for RLPs has been developed (2). This method uses two monoclonal antibodies, to human apoB-100 and apoA-I, respectively, to remove most of the apoB-100-containing lipoproteins

Apolipoprotein A5 (apoA5), an important determinant of plasma triglyceride (TG) levels, has been recently reported to modulate TG metabolism in hepatocytes. In this study, we investigated whether apoA5 can be internalized by adipocytes and regulate cellular TG storage. Human preadipocytes, derived from subcutaneous adipose tissue of patients undergoing abdominal surgery, were differentiated into mature adipocytes. Pulse-chase experiments revealed that apoA5 was internalized into human adipocytes, and ∼70% of the apoA5 internalized during the pulse remained intracellular within a 24-h chase, while 30% was degraded. Preincubation with heparin and the receptor-associated protein, both of which prevented the apoA5 interaction with members of the low-density lipoprotein receptor gene family, markedly reduced the uptake of apoA5 by 61% and 52%, respectively, which were subsequently confirmed by Western blot analysis. Using confocal microscopy, we demonstrated that labeled apoA5 surrounded lipid droplets in human adipocytes and colocalized with the known lipid droplet protein perilipin. Importantly, treatment of adipocytes with apoA5 significantly decreased cellular TG storage. In conclusion, apoA5 can be internalized by human adipocytes and may act as a novel regulator to control TG storage in human adipocytes.