Stress-induced senescence exaggerates postinjury neointimal formation in the old vasculature

Sheik J. Khan, Si Pham, Yunteo Wei, Dania Mateo, Melissa St-Pierre, Terace M. Fletcher, Roberto I. Vazquez-Padron

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

This study aims to demonstrate the role of stress-induced senescence in aged-related neointimal formation. We demonstrated that aging increases senescence-associated β-galactosidase activity (SA-β-Gal) after vascular injury and the subsequent neointimal formation (neointima-to-media ratio: 0.8 ± 0.2 vs. 0.54 ± 0.15) in rats. We found that senescent cells (SA-β-Gal+ p21+) were scattered throughout the media and adventitia of the vascular wall at day 7 after injury and reached their maximum number at day 14. However, senescent cells only persisted in the injured arteries of aged animals until day 30. No senescent cells were observed in the noninjured, contralateral artery. Interestingly, vascular senescent cells accumulated genomic 8-oxo-7,8-dihydrodeoxyguanine, indicating that these cells were under intense oxidative stress. To demonstrate whether senescence worsens intimal hyperplasia after injury, we seeded matrigel-embedded senescent and nonsenescent vascular smooth muscle cells around injured vessels. The neointima was thicker in arteries treated with senescent cells with respect to those that received normal cells (neointima-to-media ratio: 0.41 ± 0.105 vs. 0.26 ± 0.04). In conclusion, these results demonstrate that vascular senescence is not only a consequence of postinjury oxidative stress but is also a worsening factor for neointimal development in the aging vasculature.

Original languageEnglish (US)
Pages (from-to)H66-H74
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume298
Issue number1
DOIs
StatePublished - Jan 2010

Keywords

  • Aging
  • Neointima
  • Vascular injury
  • Vascular smooth muscle cells

ASJC Scopus subject areas

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

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