title: Low-density lipoproteins induce the renin-angiotensin system and their receptors in human endothelial cells.
abstract: Increased levels of low-density lipoproteins are well-established risk factors of endothelial dysfunction and the metabolic syndrome. In this study, we evaluated the effect of native low-density lipoprotein (nLDL) and oxidized LDL (oxLDL) on the expression of genes of the renin-angiotensin system (angiotensin-converting enzyme, ACE; angiotensin II type 1 receptor, AT(1)) and their receptors (low-density lipoprotein receptor: LDLR; lectin-like oxLDL receptor: LOX-1; toll-like receptor 4: TLR4) in primary cultures of human umbilical vein endothelial cells. ACE and AT(1) expressions were significantly increased after stimulation with nLDL and oxLDL. OxLDL receptor LOX-1 showed a maximum induction after 7 hours. Increased LOX-1 protein expression in response to oxLDL could be blocked by a LOX-1-specific antibody. TLR4 expression was increased by nLDL and oxLDL as well. We conclude that LDL and oxLDL can activate the renin-angiotensin system and their receptors LDLR, LOX-1, and TLR4 in human endothelial cells. These data suggest a novel link between hypercholesterolemia and hypertension in patients with the metabolic syndrome.
authors.affiliation: Department of Vascular Endothelium and Microcirculation, Medical Clinic and Policlinic III, University of Technology Dresden, Dresden, Germany.
authors.forename: R A
authors.initials: RA
authors.lastname: Catar
authors.forename: G
authors.initials: G
authors.lastname: Müller
authors.forename: J
authors.initials: J
authors.lastname: Heidler
authors.forename: G
authors.initials: G
authors.lastname: Schmitz
authors.forename: S R
authors.initials: SR
authors.lastname: Bornstein
authors.forename: H
authors.initials: H
authors.lastname: Morawietz
mesh_terms: D000704:Analysis of Variance; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D006937:Hypercholesterolemia / Q000378:metabolism; D006973:Hypertension / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism*; D024821:Metabolic Syndrome / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000235:genetics / Q000502:physiology*; D051127:Scavenger Receptors, Class E / Q000235:genetics / Q000378:metabolism; D018709:Statistics, Nonparametric; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism
chemical_list: D008077:Lipoproteins, LDL; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D011973:Receptors, LDL; D051127:Scavenger Receptors, Class E; D051197:Toll-Like Receptor 4; C099252:oxidized low density lipoprotein; D007703:Peptidyl-Dipeptidase A