Determinants of vascular smooth muscle cell apoptosis after balloon angioplasty injury: Influence of redox state and cell phenotype

Matthew J. Pollman, Jennifer L. Hall, Gary H. Gibbons

Research output: Contribution to journalArticle

171 Scopus citations

Abstract

We have observed that acute medial cell loss is an initial event in the response to vascular injury induced by balloon-catheter distention of the rabbit carotid artery. Numerous apoptotic medial cells were observed as early as 30 minutes after balloon inflation, and a 70% loss of cellularity was evident by 90 minutes. Balloon injury was associated with oxidative stress as reflected by a fall in glutathione levels by 63% within 30 minutes after injury. We hypothesized that balloon injury activated a redox-sensitive signaling pathway coupled to the regulation of apoptosis. Indeed, the activity of the proapoptotic signal mediator, stress-activated protein kinase, was increased severalfold within 10 minutes after injury. Moreover, modifying the vascular redox state by the administration of 1 of 2 structurally dissimilar antioxidants, N-acetyl cysteine or pyrrolidine dithiocarbamate, markedly attenuated both stress-activated protein kinase activation and the induction of apoptosis at 30 minutes. We hypothesized further that the induction of vascular smooth muscle cell apoptosis is modulated by phenotype. In contrast to medial cells, we observed that neointimal cells were relatively resistant to apoptotic death induced by angioplasty injury. This resistance to balloon injury-induced death was associated with an upregulation of the antiapoptotic mediator bcl-x(L). This study suggests that acute apoptotic cell death after vascular injury is a highly regulated process governed by cellular redox state and the relative expression of antiapoptotic genes. Angioplasty-induced vascular cell apoptosis may be an important determinant of vascular remodeling and restenosis.

Original languageEnglish (US)
Pages (from-to)113-121
Number of pages9
JournalCirculation research
Volume84
Issue number1
DOIs
StatePublished - Jan 8 1999

Keywords

  • Apoptosis
  • Balloon angioplasty
  • Bcl- x
  • Restenosis
  • Stress-activated protein kinase

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