Increased expression of Nox1 in neointimal smooth muscle cells promotes activation of matrix metalloproteinase-9

Shaoping Xu, Amy S. Shriver, Dammanahalli K. Jagadeesha, Ali H. Chamseddine, Katalin Szócs, Neal Lee Weintraub, Kathy K. Griendling, Ramesh C. Bhalla, Francis J. Miller

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Objective: Vascular injury causes neointimal hypertrophy, which is characterized by redox-mediated matrix degradation and smooth muscle cell (SMC) migration and proliferation. We hypothesized that, as compared to the adjacent medial SMCs, neointimal SMCs produce increased superoxide via NADPH oxidase, which induces redox-sensitive intracellular signaling to activate matrix metalloproteinase-9 (MMP-9). Methods and Results: Two weeks after balloon injury, rat aorta developed a prominent neointima, containing increased expression of NADPH oxidase and reactive oxygen species (ROS) as compared to the medial layer. Next, SMCs were isolated from either the neointima or the media and studied in culture. Neointimal-derived SMCs exhibited increased Nox1 expression and ROS levels as compared to medial SMCs. Neointimal SMCs had higher cell growth rates than medial SMCs. ROS-dependent ERK1/2 phosphorylation was greater in neointimal SMCs. MMP-9 activity, as detected by gel zymography, was greater in neointimal SMCs under resting and stimulated conditions and was prevented by expression of an antisense to Nox1 or treatment with an ERK1/2 inhibitor. Conclusions: Following vascular injury, the increased expression of Nox1 in SMCs within the neointima initiates redox-dependent phosphorylation of ERK1/2 and subsequent MMP-9 activation.

Original languageEnglish (US)
Pages (from-to)242-248
Number of pages7
JournalJournal of Vascular Research
Volume49
Issue number3
DOIs
StatePublished - May 1 2012

Keywords

  • Antioxidants
  • NADPH oxidases
  • Oxidative stress
  • Restenosis

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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    Xu, S., Shriver, A. S., Jagadeesha, D. K., Chamseddine, A. H., Szócs, K., Weintraub, N. L., Griendling, K. K., Bhalla, R. C., & Miller, F. J. (2012). Increased expression of Nox1 in neointimal smooth muscle cells promotes activation of matrix metalloproteinase-9. Journal of Vascular Research, 49(3), 242-248. https://doi.org/10.1159/000332958