title: Role of LDL receptor-related protein (LRP) in coronary atherosclerosis.
abstract: The development and progression of coronary atherosclerosis is influenced by a variety of genetic and environmental factors. Among the genetic factors, the cell surface receptor LRP/A2MR (LDL receptor-related protein/alpha2-macroglobulin receptor) was shown to be involved in a variety of biological processes leading to atherosclerotic plaque formation. That is why the individual expression of this receptor may, therefore, be considered as an evident predictor for coronary atherosclerosis. In this clinical ex vivo study the expression was measured by competitive RT-PCR and macroarray analysis in native monocytes. Both methods were first tested in an in vitro model using different human cells and cell lines (fibroblasts: chorion, skin; endothelial cells from umbilical cord vein; monocyte cell line: Mono-Mac-6): after stimulation with an LRP/A2MR ligand, leptin, the anticipated direct effect of this ligand, namely an increase in both receptor mRNA and protein expression, was confirmed. In disease-related ex vivo studies the mRNA and protein-expression of LRP/A2MR was investigated in 36 male patients suffering from myocardial infarction. In comparison to the control group (36 healthy male blood donors), a significant up-regulation of mRNA was detected in the myocardial infarction patient group (control: 122.3 ag/cell versus patients: 223 ag/cell; P<0.001). Investigating the LRP/A2MR protein expression a significant down-regulation of protein expression was determined in the patient group (control: 6 pg/cell versus patients: 1.6 pg/cell; P<0.001). The ratio of LRP/A2MR mRNA and protein expression is obviously an evident marker for coronary atherosclerosis, recommendable for the assessment of the individual coronary risk profile.
authors.affiliation: Institute of Human Genetics and Medical Biology, University of Halle, Magdeburger Str 2, D-06097 Halle, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Schulz
authors.forename: Gerd
authors.initials: G
authors.lastname: Birkenmeier
authors.forename: Undraga
authors.initials: U
authors.lastname: Schagdarsurengin
authors.forename: Katrin
authors.initials: K
authors.lastname: Wenzel
authors.forename: Ursula
authors.initials: U
authors.lastname: Müller-Werdan
authors.forename: Dirk
authors.initials: D
authors.lastname: Rehfeld
authors.forename: Thomas
authors.initials: T
authors.lastname: Süss
authors.forename: Andrea
authors.initials: A
authors.lastname: Kabisch
authors.forename: Karl
authors.initials: K
authors.lastname: Werdan
authors.forename: Christiane
authors.initials: C
authors.lastname: Gläser
mesh_terms: D001782:Blood Donors; D016022:Case-Control Studies; D002460:Cell Line; D002478:Cells, Cultured; D003324:Coronary Artery Disease / Q000378:metabolism*; D006801:Humans; D020738:Leptin / Q000494:pharmacology; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D011973:Receptors, LDL / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D020738:Leptin; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D012333:RNA, Messenger; D011973:Receptors, LDL