Nox2 and p47phox modulate compensatory growth of primary collateral arteries

Matthew R. DiStasi, Joseph L. Unthank, Steven J. Miller

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

The role of NADPH oxidase (Nox in both the promotion and impairment of compensatory collateral growth remains controversial because the specific Nox and reactive oxygen species involved are unclear. The aim of this study was to identify the primary Nox and reactive oxygen species associated with early stage compensatory collateral growth in young, healthy animals. Ligation of the feed arteries that form primary collateral pathways in rat mesentery and mouse hindlimb was used to assess the role of Nox during collateral growth. Changes in mesenteric collateral artery Nox mRNA expression determined by real-time PCR at 1, 3, and 7 days relative to same-animal control arteries suggested a role for Nox subunits Nox2 and p47phox. Administration of apocynin or Nox2ds-tat suppressed collateral growth in both rat and mouse models, suggesting the Nox2/p47phoxinteraction was involved. Functional significance of p47phox expression was assessed by evaluation of collateral growth in rats administered p47phoxsmall interfering RNA and in p47phox-/- mice. Diameter measurements of collateral mesenteric and gracilis arteries at 7 and 14 days, respectively, indicated no significant collateral growth compared with control rats or C57BL/6 mice. Chronic polyethylene glycol-conjugated catalase administration significantly suppressed collateral development in rats and mice, implying a requirement for H2O2. Taken together, these results suggest that Nox2, modulated at least in part by p47phox, mediates early stage compensatory collateral development via a process dependent upon peroxide generation. These results have important implications for the use of antioxidants and the development of therapies for peripheral arterial disease.

Original languageEnglish (US)
Pages (from-to)H1435-H1443
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume306
Issue number10
DOIs
StatePublished - May 15 2014

Keywords

  • Collateral artery
  • Hydrogen peroxide
  • NADPH oxidase
  • Nox2

ASJC Scopus subject areas

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

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