Histamine deficiency decreases atherosclerosis and inflammatory response in apolipoprotein e knockout mice independently of serum cholesterol level

Ke Yong Wang, Akihide Tanimoto, Xin Guo, Sohsuke Yamada, Shohei Shimajiri, Yoshitaka Murata, Yan Ding, Masato Tsutsui, Seiya Kato, Teruo Watanabe, Hiroshi Ohtsu, Ken Ichi Hirano, Kimitoshi Kohno, Yasuyuki Sasaguri

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Objective- Histamine and histamine receptors are found in atherosclerotic lesions, and their signaling and subsequent proatherogenic or proinflammatory gene expression are involved in atherogenesis. In the present study, we generated apolipoprotein E (apoE) and histamine synthesizing histidine decarboxylase double knockout (DKO) mice on a C57BL/6J (wild-type mice) background to clarify the roles of histamine in atherosclerosis. Methods and Results- Wild-type, apoE knockout (KO), and DKO mice were fed a high-cholesterol diet to analyze hyperlipidemia-induced atherosclerosis. Compared with wild-type mice, apoE-KO mice showed increased expression of histamine and its receptors, corresponding to increased atherosclerotic lesion areas and expression of inflammatory regulators, such as nuclear factor-κB, scavenger receptors, inflammatory cytokines, and matrix metalloproteinases. Histamine deficiency after deletion of histidine decarboxylase reduced atherosclerotic areas and expression of a range of the inflammation regulatory genes, but serum cholesterol levels of DKO mice were higher than those of apoE-KO mice. Conclusion- These results indicate that histamine is involved in the development of atherosclerosis in apoE-KO mice by regulating gene expression of inflammatory modulators, an action that appears to be independent of serum cholesterol levels. In addition to acute inflammatory response, histamine participates in chronic inflammation, such as hyperlipidemia-induced atherosclerosis, and might be a novel therapeutic target for the treatment of atherosclerosis.

Original languageEnglish
Pages (from-to)800-807
Number of pages8
JournalArteriosclerosis, thrombosis, and vascular biology
Volume31
Issue number4
DOIs
Publication statusPublished - 2011 Apr

Keywords

  • histamine
  • histidine decarboxylase
  • hyperlipidemia-induced atherosclerosis
  • inflammation
  • matrix metalloproteinase

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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    Wang, K. Y., Tanimoto, A., Guo, X., Yamada, S., Shimajiri, S., Murata, Y., Ding, Y., Tsutsui, M., Kato, S., Watanabe, T., Ohtsu, H., Hirano, K. I., Kohno, K., & Sasaguri, Y. (2011). Histamine deficiency decreases atherosclerosis and inflammatory response in apolipoprotein e knockout mice independently of serum cholesterol level. Arteriosclerosis, thrombosis, and vascular biology, 31(4), 800-807. https://doi.org/10.1161/ATVBAHA.110.215228