title: Ablation of the bach1 gene leads to the suppression of atherosclerosis in bach1 and apolipoprotein E double knockout mice.
abstract: This study was designed to determine whether Bach1 gene ablation leads to suppression of atherosclerosis in apolipoprotein E (Apo E)/Bach1 double knockout (DKO) mice. Apo E/Bach1 DKO mice were generated by intercrossing Apo E knockout (KO) and Bach1 KO mice. The animals were fed a high-fat diet for 8 weeks, and the atherosclerotic plaques in the thoracic and abdominal aorta were visualized by oil red O staining. In DKO mice, the total plaque area was reduced by 32% compared with that in Apo E KO mice. In DKO mice, heme oxygenase-1 (HO-1) was upregulated in the endothelium and, to a lesser extent, in vascular smooth muscles. In atherosclerotic plaques in Apo E KO mice and DKO mice, HO-1 was abundantly expressed in the endothelium and macrophages. Urine excretion of 8-iso-prostaglandin (PG) F2alpha, a marker for lipid peroxidation, was reduced in DKO mice compared with that in Apo E KO mice. The effects of Bach1 ablation on the plaque area and 8-iso-PG F2alpha excretion were almost completely abolished by treating DKO mice with Sn protoporphyrin, an inhibitor of HO activity. Disruption of the Bach1 gene in Apo E KO mice caused inhibition of atherosclerosis through upregulation of HO-1. Inhibition of Bach1, conversely, may be a novel therapeutic strategy to treat atherosclerotic diseases.
authors.affiliation: Department of Medicine and Molecular Science, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Watari
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Andrei
authors.initials: A
authors.lastname: Brydun
authors.forename: Takafumi
authors.initials: T
authors.lastname: Ishida
authors.forename: Shinji
authors.initials: S
authors.lastname: Mito
authors.forename: Masao
authors.initials: M
authors.lastname: Yoshizumi
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Igarashi
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Chayama
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ohshima
authors.forename: Ryoji
authors.initials: R
authors.lastname: Ozono
mesh_terms: D000818:Animals; D001012:Aorta, Abdominal / Q000378:metabolism / Q000473:pathology; D001013:Aorta, Thoracic / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics*; D050197:Atherosclerosis / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006973:Hypertension / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology; D015854:Up-Regulation / Q000502:physiology
chemical_list: D001057:Apolipoproteins E; C486316:Bach1 protein, mouse; D050976:Basic-Leucine Zipper Transcription Factors; D051547:Heme Oxygenase-1