title: Egr-1 deficiency in bone marrow-derived cells reduces atherosclerotic lesion formation in a hyperlipidaemic mouse model.
abstract: OBJECTIVE
  Early growth response gene-1 (Egr-1) regulates the expression of genes important to cardiovascular disease. Within atherosclerotic lesions, Egr-1 is expressed in smooth muscle cells, endothelial cells, and macrophages. Since macrophages play a pivotal role in atherosclerotic lesion initiation and progression, this study investigated the effects of Egr-1 deficiency within bone marrow-derived cells on the development of atherosclerosis in a hyperlipidaemic mouse model.
  
  
  RESULTS
  Bone marrow from Egr-1-deficient mice and wild-type controls was transplanted into lethally irradiated LDL receptor null mice. After 26 weeks on a high fat diet, atherosclerotic lesion size within the aortic sinus of recipients was evaluated. Mice receiving Egr-1-deficient bone marrow had significantly decreased lesion size compared with controls. Lesions of these mice contained fewer macrophages and had reduced expression of vascular cell adhesion molecule-1 (VCAM-1), tissue factor, as well as transforming growth factor receptor type II, which are target genes of Egr-1. These results were validated by in vitro analysis of Egr-1-deficient peritoneal macrophages which, after lipopolysaccharide stimulation, had decreased VCAM-1 and tissue factor mRNA expression compared with wild-type controls.
  
  
  CONCLUSIONS
  This study demonstrates that bone marrow-derived Egr-1 promotes macrophage accumulation, atherosclerotic lesion development, and lesion complexity.
authors.affiliation: Department of Internal Medicine III, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Albrecht
authors.forename: Michael R
authors.initials: MR
authors.lastname: Preusch
authors.forename: Götz
authors.initials: G
authors.lastname: Hofmann
authors.forename: Samuel
authors.initials: S
authors.lastname: Morris-Rosenfeld
authors.forename: Erwin
authors.initials: E
authors.lastname: Blessing
authors.forename: Michael E
authors.initials: ME
authors.lastname: Rosenfeld
authors.forename: Hugo A
authors.initials: HA
authors.lastname: Katus
authors.forename: Florian
authors.initials: F
authors.lastname: Bea
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism* / Q000473:pathology; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D001854:Bone Marrow Cells / Q000378:metabolism*; D016026:Bone Marrow Transplantation; D004195:Disease Models, Animal; D051766:Early Growth Response Protein 1 / Q000172:deficiency* / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D006949:Hyperlipidemias / Q000150:complications / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008055:Lipids / Q000097:blood; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011828:Radiation Chimera; D000077294:Receptor, Transforming Growth Factor-beta Type II; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D013925:Thromboplastin / Q000378:metabolism; D013997:Time Factors; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D014916:Whole-Body Irradiation
chemical_list: D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D008055:Lipids; D012333:RNA, Messenger; D011973:Receptors, LDL; D018125:Receptors, Transforming Growth Factor beta; D019010:Vascular Cell Adhesion Molecule-1; D013925:Thromboplastin; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II