Effect of nitric oxide on neointimal hyperplasia based on sex and hormone status

Melissa E. Hogg, Vinit N. Varu, Ashley K. Vavra, Daniel A. Popowich, Monisha N. Banerjee, Janet Martinez, Qun Jiang, Joseph E. Saavedra, Larry K. Keefer, Melina R. Kibbe

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Nitric oxide (NO)-based therapies decrease neointimal hyperplasia; however, studies have been performed only in male animal models. Thus, we sought to evaluate the effect of NO on vascular smooth muscle cells (VSMC) in vitro and neointimal hyperplasia in vivo based on sex and hormone status. In hormone-replete medium, male VSMC proliferated at greater rates than female VSMC. In hormone-depleted medium, female VSMC proliferated at greater rates than male VSMC. However, in both hormone environments, NO inhibited proliferation and migration to a greater extent in male compared to female VSMC. These findings correlated with greater G0/G1 cell cycle arrest and changes in cell cycle protein expression in male compared to female VSMC after exposure to NO. Next, the rat carotid artery injury model was used to assess the effect of NO on neointimal hyperplasia in vivo. Consistent with the in vitro data, NO was significantly more effective at inhibiting neointimal hyperplasia in hormonally intact males compared to females using weight-based dosing. An increased weight-based dose of NO in females was able to achieve efficacy equal to that in males. Surprisingly, NO was less effective at inhibiting neointimal hyperplasia in castrated animals of both sexes. In conclusion, these data suggest that NO inhibits neointimal hyperplasia more effectively in males compared to females and in hormonally intact compared to castrated rats, indicating that the effects of NO in the vasculature may be sex- and hormone-dependent.

Original languageEnglish (US)
Pages (from-to)1065-1074
Number of pages10
JournalFree Radical Biology and Medicine
Volume50
Issue number9
DOIs
StatePublished - May 1 2011

Keywords

  • Cell cycle
  • Free radicals
  • Hormones
  • Neointimal hyperplasia
  • Nitric oxide
  • Vascular smooth muscle proliferation

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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