Effects of genetic ablation of bach1 upon smooth muscle cell proliferation and atherosclerosis after cuff injury

Shinji Omura, Hiroshi Suzuki, Mamoru Toyofuku, Ryoji Ozono, Nobuoki Kohno, Kazuhiko Igarashi

Research output: Contribution to journalArticlepeer-review

41 Citations (Scopus)

Abstract

Bach1 is a transcriptional repressor of the cytoprotective enzyme heme oxygenase-1 (HO-1). Although HO-1 protects against atherosclerosis, the function f Bach1 in this process is poorly understood. We isolated peritoneal macrophages and aortic smooth muscle cells (SMC) from wild-type and bach1-deficient mice. bach1-deficient macrophages expressed increased levels of HO-1 and showed elevated phagocytic activity when incubated with 0.75 μm microspheres. In SMC, bach1-ablation resulted in increased expression of HO-1 and decreased proliferation in bromodeoxyuridine incorporation assay as compared with wild-type cells.The up-regulated phagocytic activity and reduce SMC proliferation of bach1-deficient cells were not restored by Zinc (II) protoporphyrin IX, an ihibitor HO, suggesting that HO-independent mechanisms are also involved in the regulation of phagocytosis of macrophages and proliferation of SMC by Bach1. In wild-type mice, cuff placement around femoral artery caused pronounced intimal proliferation without affecting the media, thus resulting in intimal to medial (I/M) volume ratio of 65.6%. bach1-deficient mice had less degree of intimal growth (I/M ratio of 45.6%).These results indicate that Bach1 plays a critical role in the regulation of HO-1 expression, macrophage function, SMC proliferation and neointimal formation. Bach1 may regulate gene expression in these cells during in inflammation and atherogenesis.

Original languageEnglish
Pages (from-to)277-285
Number of pages9
JournalGenes to Cells
Volume10
Issue number3
DOIs
Publication statusPublished - 2005 Mar
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

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