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

• Verfasst von: Albrecht, Claudia [VerfasserIn]
• Verfasst von: Preusch, Michael [VerfasserIn]
• Verfasst von: Hofmann, Götz-Ulrich [VerfasserIn]
• Verfasst von: Morris-Rosenfeld, Samuel [VerfasserIn]
• Verfasst von: Blessing, Erwin [VerfasserIn]
• Verfasst von: Rosenfeld, Michael E. [VerfasserIn]
• Verfasst von: Katus, Hugo [VerfasserIn]
• Verfasst von: Bea, Florian [VerfasserIn]
• Titel: Egr-1 deficiency in bone marrow-derived cells reduces atherosclerotic lesion formation in a hyperlipidaemic mouse model
• Verf.angabe: Claudia Albrecht, Michael R. Preusch, Götz Hofmann, Samuel Morris-Rosenfeld, Erwin Blessing, Michael E. Rosenfeld, Hugo A. Katus, and Florian Bea
• E-Jahr: 2010
• Jahr: 28 January 2010
• Umfang: 9 S.
• Fussnoten: Gesehen am 16.11.2022
• Titel Quelle: Enthalten in: Cardiovascular research
• Ort Quelle: Oxford : Oxford University Press, 1967
• Jahr Quelle: 2010
• Band/Heft Quelle: 86(2010), 2, Seite 321-329
• ISSN Quelle: 1755-3245
• DOI: doi:10.1093/cvr/cvq032
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1822665817

Abstract

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.