Crucial vasculoprotective role of the whole nitric oxide synthase system in vascular lesion formation in mice: Involvement of bone marrow-derived cells

Yumi Furuno, Tsuyoshi Morishita, Yumiko Toyohira, Sohsuke Yamada, Susumu Ueno, Naoya Morisada, Kazunari Sugita, Katsuhiko Noguchi, Mayuko Sakanashi, Hironori Miyata, Akihide Tanimoto, Yasuyuki Sasaguri, Hiroaki Shimokawa, Yutaka Otsuji, Nobuyuki Yanagihara, Masahito Tamura, Masato Tsutsui

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

Although all three nitric oxide (NO) synthases (nNOS, iNOS, and eNOS) are expressed in injured arteries, it remains to be elucidated the role of the NOSs in their entirety in the vascular lesion formation. We addressed this issue in mice deficient in all NOS genes. Vascular injury was induced by permanent ligation of a unilateral carotid artery in wild-type (WT), singly, and triply NOS -/- mice. Two weeks after the procedure, constrictive vascular remodeling and neointimal formation were recognized in the ligated arteries. While constrictive remodeling was noted in the nNOS -/- and iNOS -/- genotypes, it was most accelerated in the n/i/eNOS -/- genotype. While neointimal formation was evident in the eNOS -/- and nNOS -/- genotypes, it was also most aggravated in the n/i/eNOS -/- genotype. Those lesions were reversed by long-term treatment with isosorbide dinitrate, a NO donor. Finally, we examined the involvement of bone marrow-derived cells in the vascular lesion formation. Bone marrow from the WT, singly, or triply NOS -/- mice was transplanted into the WT mice, and then the carotid ligation was performed. Intriguingly, constrictive remodeling and neointimal formation were both similarly most exacerbated in the case of the n/i/eNOS -/- bone marrow transplantation. These results indicate that the complete disruption of all the NOS genes causes markedly accelerated vascular lesion formation caused by blood flow disruption in mice in vivo, demonstrating the crucial vasculoprotective role of the whole endogenous NOS system. Our findings also suggest that the NOS system in bone marrow-derived cells may be involved in this vasculoprotective mechanism.

Original languageEnglish
Pages (from-to)350-359
Number of pages10
JournalNitric Oxide - Biology and Chemistry
Volume25
Issue number3
DOIs
Publication statusPublished - 2011 Oct 30

Keywords

  • Arteriosclerosis
  • Mice
  • Nitric oxide
  • Nitric oxide synthase
  • Vascular remodeling

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Clinical Biochemistry
  • Cancer Research

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