Vascular endothelial cell-derived endothelin-1 mediates vascular inflammation and neointima formation following blood flow cessation

Dyah W. Anggrahini, Noriaki Emoto, Kazuhiko Nakayama, Bambang Widyantoro, Suko Adiarto, Naoko Iwasa, Hidemi Nonaka, Yoshiyuki Rikitake, Yaz Y. Kisanuki, Masashi Yanagisawa, Ken Ichi Hirata

Research output: Contribution to journalArticle

67 Scopus citations

Abstract

Aims: Although endothelin-1 (ET-1) has been suggested to contribute to the pathogenesis of neointima formation and atherosclerosis, the individual roles of ET-1 derived from certain cell types in this disease remain unclear. In this study, we determined the role of vascular endothelial ET-1 on vascular inflammation and neointima formation using vascular endothelial ET-1-knockout [ET-1f/f; Tie2-Cre (+)] mice. Methods and results: Intimal hyperplasia was induced by complete ligation of the left carotid artery in 12-week-old male ET-1f/f;Tie2-Cre (+) mice (n = 35) and the wild-type (WT) littermates (n = 34). Following this intervention, neointima formation was reduced in ET-1f/f;Tie2-Cre (+) mice compared with the WT mice, independent of the difference in blood pressure. This reduction was associated with a decrease in inflammatory cell recruitment to the vessel wall, which was accompanied by reduced expression levels of endothelial adhesion molecules as well as chemokines and a decrease in vascular smooth muscle cell proliferation. Conclusion: The results of our study provide direct evidence for the role of vascular endothelial ET-1 in mediating vascular inflammation and neointima formation following vascular injury in addition to promoting vasoconstriction and cell proliferation. Furthermore, this study suggests a strategy for the efficient design of ET receptor antagonists with targeted inhibition of ET-1 signalling in vascular endothelial cells.

Original languageEnglish (US)
Pages (from-to)143-151
Number of pages9
JournalCardiovascular Research
Volume82
Issue number1
DOIs
StatePublished - Apr 1 2009

Keywords

  • Atherosclerosis
  • Carotid ligation
  • Endothelin-1
  • Inflammation
  • Neointima formation

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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  • Cite this

    Anggrahini, D. W., Emoto, N., Nakayama, K., Widyantoro, B., Adiarto, S., Iwasa, N., Nonaka, H., Rikitake, Y., Kisanuki, Y. Y., Yanagisawa, M., & Hirata, K. I. (2009). Vascular endothelial cell-derived endothelin-1 mediates vascular inflammation and neointima formation following blood flow cessation. Cardiovascular Research, 82(1), 143-151. https://doi.org/10.1093/cvr/cvp026