title: Lipocalin (LCN) 2 Mediates Pro-Atherosclerotic Processes and Is Elevated in Patients with Coronary Artery Disease.
abstract: BACKGROUND
  Lipocalin (LCN) 2 is associated with multiple acute and chronic inflammatory diseases but the underlying molecular and cellular mechanisms remain unclear. Here, we investigated whether LCN2 is released from macrophages and contributes to pro-atherosclerotic processes and whether LCN2 plasma levels are associated with the severity of coronary artery disease progression in humans.
  
  
  RESULTS
  In an autocrine-paracrine loop, tumor necrosis factor (TNF)-α promoted the release of LCN2 from murine bone-marrow derived macrophages (BMDM) and vice versa. Moreover, LCN2 stimulation of BMDM led to up-regulation of M1 macrophage markers. In addition, enhanced migration of monocytic J774A.1 cells towards LCN2 was observed. Furthermore, LCN2 increased the expression of the scavenger receptors Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) as well as scavenger receptor class A-1 (SRA-1) and induced the conversion of macrophages to foam cells. In atherosclerotic lesions of low density lipoprotein receptor-deficient (ldlr-/-) mice fed a high fat, high cholesterol diet, LCN2 was found to be co-localized with macrophages in the shoulder region of the atherosclerotic plaque. In addition, LCN2 plasma levels were significantly increased in plasma samples of these mice. Finally, LCN2 plasma levels correlated with the severity of coronary artery disease (CAD) in patients as determined by coronary angiography.
  
  
  CONCLUSIONS
  Here we demonstrated that LCN2 plays a pivotal role in processes involved in atherogenesis by promoting polarization and migration of monocytic cells and development of macrophages towards foam cells. Moreover, LCN2 may be used as a prognostic marker to determine the status of CAD progression.
authors.affiliation: Department of Cardiology and Angiology, Philipps-University Marburg, Marburg, Germany.
authors.forename: Raghav
authors.initials: R
authors.lastname: Oberoi
authors.affiliation: Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.
authors.forename: Eskindir P
authors.initials: EP
authors.lastname: Bogalle
authors.affiliation: Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.
authors.forename: Lukas A
authors.initials: LA
authors.lastname: Matthes
authors.affiliation: Department of Cardiology and Angiology, Philipps-University Marburg, Marburg, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Schuett
authors.affiliation: Department of Cardiology and Angiology, Philipps-University Marburg, Marburg, Germany.
authors.forename: Ann-Kathrin
authors.initials: AK
authors.lastname: Koch
authors.affiliation: Department of Cardiology and Angiology, Philipps-University Marburg, Marburg, Germany.
authors.forename: Karsten
authors.initials: K
authors.lastname: Grote
authors.affiliation: Department of Cardiology and Angiology, Philipps-University Marburg, Marburg, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Schieffer
authors.affiliation: Department of Cardiology and Angiology, Philipps-University Marburg, Marburg, Germany.
authors.forename: Jutta
authors.initials: J
authors.lastname: Schuett
authors.affiliation: Department of Cardiology and Angiology, Philipps-University Marburg, Marburg, Germany.
authors.forename: Maren
authors.initials: M
authors.lastname: Luchtefeld
mesh_terms: D000209:Acute-Phase Proteins / Q000235:genetics; D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000097:blood* / Q000000981:diagnostic imaging / Q000235:genetics; D005260:Female; D005487:Foam Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D000071068:Lipocalin-2; D054834:Lipocalins / Q000097:blood* / Q000235:genetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D015513:Oncogene Proteins / Q000097:blood* / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000097:blood* / Q000235:genetics; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism; D051117:Scavenger Receptors, Class A / Q000235:genetics / Q000378:metabolism; D051127:Scavenger Receptors, Class E / Q000235:genetics / Q000378:metabolism
chemical_list: D000209:Acute-Phase Proteins; C489506:LCN2 protein, human; C573412:LDLR protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; C495139:MSR1 protein, human; C495137:OLR1 protein, human; C495138:Olr1 protein, mouse; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D011973:Receptors, LDL; D051117:Scavenger Receptors, Class A; D051127:Scavenger Receptors, Class E; C071332:Lcn2 protein, mouse