Detection, Quantification, and Characterization of Potentially Atherogenic Triglyceride-Rich Remnant Lipoproteins

Abstract

Abstract-Triglyceride-rich lipoprotein (TRL) remnants are formed in the circulation when apolipoprotein (apo) B-48 -containing chylomicrons of intestinal origin or apoB-100 -containing VLDL of hepatic origin are converted by lipoprotein lipase, and to a lesser extent by hepatic lipase, into smaller and more dense particles. Compared with their nascent precursors, TRL remnants are depleted of triglyceride, phospholipid, and C apolipoproteins and are enriched in cholesteryl esters and apoE. They can thus be identified, separated, and/or quantified in plasma according to their density, charge, size, specific lipid components, apolipoprotein composition, and/or apolipoprotein immunospecificity. Each of these approaches has contributed to our current understanding of the compositional characteristics of TRL remnants and their potential to promote atherosclerosis. An ongoing search is nevertheless under way for more accurate and clinically applicable remnant lipoprotein assays that will be able to better define coronary artery disease risk in patients with hypertriglyceridemia.

Triglyceride-rich lipoprotein lipolysis releases neutral and oxidized FFAs that induce endothelial cell inflammation

“…TGRL lipolysis during the postprandial state releases excess FFAs in the immediate proximity of the endothelium, which may cause endothelial injury (11) and subsequent endothelial dysfunction (32). In addition, TGRL remnants derived from TGRL lipolysis are themselves atherogenic (33,34), Endothelial cell cultures in 12-well plates were treated for 2 h with individual lipids isolated from VLDL (50 mg/dl TG) with or without 30 min incubation with LpL (2 U/ml). Each fraction was isolated from VLDL, evaporated, redissolved, and delivered to cells in a PBS vehicle (5 ml).…”

Effects of Atorvastatin Therapy on the Low-Density Lipoprotein Subfraction, Remnant-Like Particles Cholesterol, and Oxidized Low-Density Lipoprotein Within 2 Weeks in Hypercholesterolemic Patients

“…30 Increased RLP-C concentrations have been reported to be a significant and independent risk factor for coronary artery disease. 31 Recently, Stein et al 32 reported that RLP-C concentrations are significantly reduced after 6 weeks of therapy with atorvastatin or simvastatin, but not with pravastatin.…”

Ezetimibe: cholesterol lowering and beyond

“…RLP-C is included in the measurement of non-HDL-C levels, a secondary treatment target after LDL-C lowering in hypertriglyceridemic patients (>200 mg/dl), as mentioned previously [74]. Additionally, following isolation from plasma, RLPs can be further characterized by various methods based on density, size, charge, apolipoprotein composition and immunoabsorption [108,109].…”