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...
Gespeichert in:
| Hauptverfasser: | , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
28 January 2010
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| 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
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| Verfasserangaben: | Claudia Albrecht, Michael R. Preusch, Götz Hofmann, Samuel Morris-Rosenfeld, Erwin Blessing, Michael E. Rosenfeld, Hugo A. Katus, and Florian Bea |
MARC
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| 520 | |a 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. | ||
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