Ablation of the Bach1 gene leads to the suppression of atherosclerosis in Bach1 and apolipoprotein E double knockout mice

Yuichiro Watari, Yoshiyuki Yamamoto, Andrei Brydun, Takafumi Ishida, Shinji Mito, Masao Yoshizumi, Kazuhiko Igarashi, Kazuaki Chayama, Tetsuya Ohshima, Ryoji Ozono

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23 Citations (Scopus)

Abstract

This study was designed to determine whether Bach1 gene ablation leads to suppression of atherosclerosis in apolipoprotein E (Apo EVBach1 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 endothellum and macrophages. Urine excretion of 8-iso-prostaglandin (PG) F2α, 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 F2α 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.

Original languageEnglish
Pages (from-to)783-792
Number of pages10
JournalHypertension Research
Volume31
Issue number4
DOIs
Publication statusPublished - 2008 Apr

Keywords

  • Apolipoprotein E knockout mice
  • Atherosclerosis
  • Bach1 knockout mice
  • Heme oxgenase-1

ASJC Scopus subject areas

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

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    Watari, Y., Yamamoto, Y., Brydun, A., Ishida, T., Mito, S., Yoshizumi, M., Igarashi, K., Chayama, K., Ohshima, T., & Ozono, R. (2008). Ablation of the Bach1 gene leads to the suppression of atherosclerosis in Bach1 and apolipoprotein E double knockout mice. Hypertension Research, 31(4), 783-792. https://doi.org/10.1291/hypres.31.783