Beneficial effect of a short-acting NO donor for the prevention of neointimal hyperplasia

Charles G. Pearce, Samer F. Najjar, Muneera R. Kapadia, Jozef Murar, Jason Eng, Brian Lyle, Oliver O. Aalami, Qun Jiang, Joseph A. Hrabie, Joseph E. Saavedra, Larry K. Keefer, Melina R. Kibbe*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

68 Scopus citations


Nitric oxide (NO)-based therapies effectively inhibit neointimal hyperplasia in animal models of arterial injury and bypass grafting, but are not available clinically. We created a simple, effective, locally applied NO-eluting therapy to prevent restenosis after vascular procedures. We investigated the efficacy of perivascular delivery of two distinctly different diazeniumdiolate NO donors, 1-[2-(carboxylato)pyrrolidin-1-yl]diazen-1-ium-1,2-diolate (PROLI/NO) (short half-life) and diazeniumdiolated poly(acrylonitrile) (PAN/NO) (long half-life), in powder or gel form (30% poloxamer 407), at inhibiting neointimal hyperplasia using the rat carotid artery injury model. Two weeks postinjury, all of the NO-eluting therapies successfully reduced neointimal hyperplasia. However, most dramatically, PROLI/NO powder reduced intimal area by 91.2% (p < 0.05) versus injury alone. PROLI/NO powder was noted to reduce the medial area (40.2% vs injury alone, p < 0.05), whereas other groups showed no such effect. Three days postinjury, each NO treatment group significantly reduced cellular proliferation. However, inflammatory markers revealed a distinct pattern: PAN/NO groups displayed increased leukocyte infiltration (p < 0.05), whereas PROLI/NO groups displayed less macrophage infiltration (p < 0.05). In conclusion, perivascular delivery of diazeniumdiolate NO donors in powder or gel form effectively inhibits neointimal hyperplasia. Application of short-acting PROLI/NO powder most effectively inhibited neointimal hyperplasia and inflammation and may represent a simple, clinically applicable NO-eluting therapy to prevent neointimal hyperplasia and restenosis after open vascular interventions.

Original languageEnglish (US)
Pages (from-to)73-81
Number of pages9
JournalFree Radical Biology and Medicine
Issue number1
StatePublished - Jan 1 2008


  • Arterial injury
  • Free radicals
  • Neointimal hyperplasia
  • Nitric oxide
  • Perivascular
  • Vascular smooth muscle cell proliferation

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)


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