Inhibition of inducible nitric oxide synthase promotes vein graft neoadventitial inflammation and remodeling

J. Wu, R.M. Wadsworth, S. Kennedy

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Grafting veins into the arterial circulation causes endothelial damage and neointimal hyperplasia. However, the remodelling of vein grafts and the contribution of the endothelium is not well understood. Since nitric oxide (NO) has a crucial role in vascular function, we investigated the importance of NO synthases (NOSs) in vein graft re-endothelialization and remodelling in this study. Mouse isogenic vena cava was grafted into the carotid artery. Progressive remodelling of the grafted veins was evidenced by re-endothelialization at 2 weeks and subsequent appearance of vasomotor function at 4 weeks. Pharmacological inhibition of inducible NOS (iNOS) with the specific inhibitor 1400W, administered between 2 and 4 weeks after grafting, when re-endothelialization was complete, resulted in neoadventitial inflammation, neoadventitial thickening and impaired functional remodelling. Completion of re-endothelialization is pivotal in vein graft remodelling in the mouse and is associated with a series of changes in inflammation, proliferation and initiation
of vascular functional remodelling. After re-endothelial-ization, iNOS pregulation may be an important mechanism to prevent secondary neoadventitial inflammation and preserve ongoing functional remodelling. iNOS activity could therefore be beneficial for long-term patency of the vein graft.
LanguageEnglish
Pages141-149
Number of pages9
JournalJournal of Vascular Research
Volume48
DOIs
Publication statusPublished - 8 Oct 2010

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Nitric Oxide Synthase Type II
Veins
Inflammation
Transplants
Nitric Oxide Synthase
Venae Cavae
Carotid Arteries
Endothelium
Hyperplasia
Blood Vessels
Nitric Oxide
Pharmacology

Keywords

  • vascular research
  • vein graft
  • endothelium
  • adventitia
  • neointima

Cite this

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Inhibition of inducible nitric oxide synthase promotes vein graft neoadventitial inflammation and remodeling. / Wu, J.; Wadsworth, R.M.; Kennedy, S.

In: Journal of Vascular Research, Vol. 48, 08.10.2010, p. 141-149.

Research output: Contribution to journalArticle

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