title: Disruption of endothelial barrier function by lipolytic remnants of triglyceride-rich lipoproteins.
abstract: Remnants, resulting from the lipolysis of triglyceride-rich lipoproteins, injured cultured endothelial cells and resulted in decreased barrier function of the vascular endothelium. Endothelial cells were cultured on micropore filters. Albumin transfer across endothelial cell monolayers was measured after a 24-h exposure to media enriched with control or in vitro-lipolyzed samples of various hypertriglyceridemic (HTG) sera and its isolated lipoprotein (VLDL, LDL and HDL) and serum free protein (d greater than 1.21 g/ml) fractions. Compared with control cultures, neither control HTG serum nor its isolated lipoprotein and serum-free protein fractions had any effect on albumin transfer. In contrast, lipolyzed HTG (L-HTG) serum and all of its isolated lipoprotein fractions (L-VLDL, L-IDL, L-LDL and L-HDL) caused a marked decrease in endothelial barrier function, evidenced by a significant increase in albumin transfer across endothelial monolayers. The L-IDL and L-HDL fractions were more effective in increasing albumin transfer than the L-VLDL and L-LDL fractions. The extent of the L-IDL and L-HDL mediated increases in albumin transfer was concentration dependent. An exposure of 12 h was required for L-HDL to increase albumin transfer. The L-HDL mediated increase in albumin transfer was reversible only after a 12-h exposure at low concentrations. The free protein fraction from L-HTG serum had no significant effect on the barrier function of endothelial cells. The presence of normolipidemic HDL in culture medium prevented disruption of the endothelial barrier induced by L-IDL but not by L-HDL. The decrease in endothelial barrier function induced by lipolyzed samples of HTG serum or lipoproteins appeared to be correlated with the level of free fatty acids contained in lipolytic remnants. Enrichment of LDL, and in particular HDL, with fatty acid significantly increased albumin transfer. Compared with lipolyzed samples, sera/lipoproteins oxidized in vitro by Cu2+ ions had little effect on endothelial barrier function, which did not correlate with their respective thiobarbituric acid-reacting substance (TBARS) values. TBARS remained within normal range after L-HDL incubation with endothelial cells for up to 48 h. At most concentrations tested, exposure to lipolyzed but not oxidized lipoproteins resulted in morphological perturbations of cell monolayers. These data suggest that lipolytic remnants of triglyceride-rich lipoproteins may play an important role in the development of atherosclerosis by decreasing the barrier function of the vascular endothelium. The remnant-induced injury of the arterial wall may permit the entry of cholesterol-rich lipolytic remnants as well as LDL into the arterial wall.
authors.affiliation: Department of Nutrition and Food Science, University of Kentucky, Lexington 40506-0054.
authors.forename: B
authors.initials: B
authors.lastname: Hennig
authors.forename: B H
authors.initials: BH
authors.lastname: Chung
authors.forename: B A
authors.initials: BA
authors.lastname: Watkins
authors.forename: A
authors.initials: A
authors.lastname: Alvarado
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003470:Culture Media; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D015228:Hypertriglyceridemia / Q000097:blood; D008066:Lipolysis; D008074:Lipoproteins / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D053419:Lipoproteins, IDL; D012709:Serum Albumin / Q000493:pharmacokinetics; D013552:Swine; D013997:Time Factors; D014280:Triglycerides / Q000378:metabolism / Q000502:physiology*
chemical_list: D003470:Culture Media; D008074:Lipoproteins; D053419:Lipoproteins, IDL; D012709:Serum Albumin; D014280:Triglycerides