Triacylglycerol-rich lipoproteins alter the secretion, and the cholesterol-effluxing function, of apolipoprotein E-containing lipoprotein particles from human (THP-1) macrophages.
Elevated plasma levels of triacylglycerol-rich lipoproteins (TGRLP) are associated with increased risk of atherogenesis and abnormal reverse cholesterol transport, as illustrated in Type II diabetes. Here we examine the effect of plasma triacylglycerol-rich or cholesteryl ester-rich lipoproteins on the secretion of nascent apolipoprotein E (apoE)-containing lipoprotein E (LpE) particles by human (THP-1) macrophages. As expected, preincubation with low-density lipoprotein (LDL) yielded small but significant increases in total cellular cholesterol content and also the secretion of apoE by macrophages. By contrast, preincubation with TGRLP resulted in higher, dose-dependent, increases in apoE secretion that reflected, but were not dependent on, cellular triacylglycerol accumulation. Secreted apoE was incorporated into a pre-beta migrating LpE fraction that differed in lipid composition and flotation density depending on preincubation conditions. Specifically, the LpE-containing lipoprotein fraction produced by macrophages preincubated with TGRLP was cholesterol-poor, markedly heterogeneous and of higher peak flotation density (d 1.14-1.18) when compared with particles produced after preincubation with LDL. Both the conditioned medium and the isolated (d<1.21) LpE-containing fraction, yielded by macrophages preincubated with TGRLP, seemed poorer at inducing cholesterol efflux than the equivalent fractions from cells preincubated with LDL, as judged by [(3)H]cholesterol efflux from untreated 'naïve' macrophages. Thus, although the interaction of TGRLP with macrophages can enhance apoE output from these cells, the LpE particles produced seem to be relatively inefficient mediators of cholesterol efflux. These factors might contribute to the increased risk of atherosclerosis in individuals with Type II diabetes.
Lindholm
E M
EM
Department of Biochemistry and Molecular Biology, Royal Free and University College Medical School of University College London, Royal Free Campus, Rowland Hill Street, London NW3 2PF, UK.
Palmer
A M
AM
Graham
A
A
D001057:Apolipoproteins E / Q000378:metabolism*; D001161:Arteriosclerosis / Q000209:etiology / Q000378:metabolism; D001693:Biological Transport, Active / Q000187:drug effects; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism; D003925:Diabetic Angiopathies / Q000209:etiology / Q000378:metabolism; D006801:Humans; D008074:Lipoproteins / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D012307:Risk Factors; D014280:Triglycerides / Q000378:metabolism*
D001057:Apolipoproteins E; D008074:Lipoproteins; D014280:Triglycerides; D002784:Cholesterol