In vitro production of beta-very low density lipoproteins and small, denselow density lipoproteins in mildly hypertriglyceridemic plasma: role of activities of lecithin : cholester acyltransferase, cholesterylester transferproteins and lipoprotein lipase

As a model for the formation of B-very low density lipoproteins (VLDL) and small, dense LDL by the intraplasma metabolic activities in vivo, lipoprote ins in fresh plasma were interacted in vitro with endogenous lecithin:chole sterol acyltransferase (LCAT) and cholesterylester transfer proteins (CETP) and subsequently with purified lipoprotein lipase (LpL). The LCAT and CETP reactions in a mildly hypertriglyceridemic (HTG) plasma at 37 degrees C fo r 18 h resulted in (I) esterification of about 45% plasma unesterified chol esterol (UC), (2) a marked increase in cholesterylester (CE) (+ 129%) and a decrease in triglyceride (TG) (- 45%) in VLDL, and (3) a marked increase o f TG (+ 341%) with a small net decrease of CE (- 3.6%) in LDL, causing a si gnificant alteration in the TG/CE of VLDL (from 8.0 to 1.9) and of LDL (fro m 0.20 to 0.93). The LDL in LCAT and CETP-reacted plasma is larger and more buoyant than that in control plasma. In vitro lipolysis of control and LCA T and CETP-reacted plasma by LpL, which hydrolyzed > 90% of VLDL-TG and abo ut 50-60% of LDL-TG, converted most of VLDL in control plasma (> 85%) but l ess than half (40%) of VLDL in LCAT and CETP-reacted plasma into the IDL-LD L density fraction and transformed the large, buoyant LDL in the LCAT and C ETP-reacted plasma into particles smaller and denser than those in the cent ral plasma. The remnants that accumulated in the VLDL density region of the postlipolysis LCAT and CETP-reacted plasma contained ape B-100 and E but l ittle or no detectable apo Cs and consisted of particles having pre-P and P -electrophoretic mobilities. The inhibition of LCAT during incubation of pl asma, which lessened the extent of alteration in VLDL and LDL core lipids, increased the extent of lipolytic removal of VLDL from the VLDL density reg ion but lowered the extent of alteration in the size and density of LDL. Th e LCAT, CETP and/or LpL-mediated alterations in the density of LDL in normo lipidemic fasting plasma were less pronounced than that in mildly HTG plasm a, but they became highly pronounced upon increase of its TG-rich lipoprote in level by the addition of preisolated VLDL or by the induction of postpra ndial lipemia.-Although the effect of LCAT, CETP and LpL reactions in non-c irculating plasma in vitro may be different from that in vivo, the above da ta suggests that the plasma TG-rich lipoprotein level and the extent of int raplasma LCAT, CETP, LpL and likely hepatic lipase (HL) reactions in vivo m ay play a role in determining the LDL phenotype. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.