Egr-1 deficiency in bone marrow-derived cells reduces atherosclerotic lesion formation in a hyperlipidaemic mouse model

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 pr...

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Hauptverfasser: Albrecht, Claudia (VerfasserIn) , Preusch, Michael (VerfasserIn) , Hofmann, Götz-Ulrich (VerfasserIn) , Morris-Rosenfeld, Samuel (VerfasserIn) , Blessing, Erwin (VerfasserIn) , Rosenfeld, Michael E. (VerfasserIn) , Katus, Hugo (VerfasserIn) , Bea, Florian (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 28 January 2010
In: Cardiovascular research
Year: 2010, Jahrgang: 86, Heft: 2, Pages: 321-329
ISSN:1755-3245
DOI:10.1093/cvr/cvq032
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1093/cvr/cvq032
Volltext
Verfasserangaben:Claudia Albrecht, Michael R. Preusch, Götz Hofmann, Samuel Morris-Rosenfeld, Erwin Blessing, Michael E. Rosenfeld, Hugo A. Katus, and Florian Bea
Beschreibung
Zusammenfassung: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.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.This study demonstrates that bone marrow-derived Egr-1 promotes macrophage accumulation, atherosclerotic lesion development, and lesion complexity.
Beschreibung:Gesehen am 16.11.2022
Beschreibung:Online Resource
ISSN:1755-3245
DOI:10.1093/cvr/cvq032