title: Effects of oxidized low-density lipoproteins on the hepatic microvasculature.
abstract: Oxidized low-density lipoproteins (oxLDLs) are involved in proinflammatory and cytotoxic events in different microcirculatory systems. The liver is an important scavenger organ for circulating oxLDLs. However, the interaction of oxLDL with the hepatic microcirculation has been poorly investigated. The present study was conducted to examine the effects of differently modified oxLDLs on the hepatic microvasculature. C57Bl/6J mice were injected intravenously with low-density lipoprotein (LDL), or LDL oxidized for 3 h (oxLDL(3)) or 24 h (oxLDL(24)), at doses resembling oxLDL plasma levels in cardiovascular disease patients. Radioiodinated ligands were used to measure blood decay and organ distribution, and nonlabeled ligands to evaluate microcirculatory responses, examined by in vivo microscopy 30-60 min after ligand injection, immunohistochemistry, and scanning and transmission electron microscopy. Mildly oxLDL (oxLDL(3)) was cleared from blood at a markedly slower rate than heavily oxLDL (oxLDL(24)), but significantly faster than LDL (P < 0.01). Injected oxLDLs distributed to liver. OxLDL effects were most pronounced in central areas of the liver lobules where oxLDL(3) elicited a significant (P < 0.05) reduction in perfused sinusoids, and both oxLDL(3) and oxLDL(24) significantly increased the numbers of swollen endothelial cells and adherent leukocytes compared with LDL (P < 0.05). OxLDL-treated livers also exhibited increased intercellular adhesion molecule (ICAM)-1 centrilobular staining. Electron microscopy showed a 30% increased thickness of the liver sinusoidal endothelium in the oxLDL(3) group (P < 0.05) and a reduced sinusoidal fenestration in centrilobular areas with increased oxidation of LDL (P for linear trend <0.05). In conclusion, OxLDL induced several acute changes in the liver microvasculature, which may lead to sinusoidal endothelial dysfunction.
authors.affiliation: Vascular Biology Research Group, Dept. of Medical Biology, Univ. of Tromsø, Norway. ana.oteiza@uit.no
authors.forename: Ana
authors.initials: A
authors.lastname: Oteiza
authors.forename: Ruomei
authors.initials: R
authors.lastname: Li
authors.forename: Robert S
authors.initials: RS
authors.lastname: McCuskey
authors.forename: Bård
authors.initials: B
authors.lastname: Smedsrød
authors.forename: Karen Kristine
authors.initials: KK
authors.lastname: Sørensen
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D007457:Iodine Radioisotopes; D007962:Leukocytes / Q000276:immunology; D008077:Lipoproteins, LDL / Q000097:blood / Q000494:pharmacology*; D008099:Liver / Q000098:blood supply* / Q000187:drug effects; D008297:Male; D051379:Mice; D008855:Microscopy, Electron, Scanning; D055806:Microvessels / Q000187:drug effects*; D014018:Tissue Distribution
chemical_list: C090509:Icam1 protein, mouse; D007457:Iodine Radioisotopes; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D018799:Intercellular Adhesion Molecule-1