Oxidative stress induces early-onset apoptosis of vascular smooth muscle cells and neointima formation in response to injury

Camilo Gomez, Laisel Martinez, Annia Mesa, Juan C. Duque, Luis A. Escobar, Si M. Pham, Roberto I Vazquez-Padron

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

The present study dissects the mechanisms underlying the rapid onset of apoptosis that precedes post injury vascular remodelling. Using the rat balloon injury model, we demonstrated that a significant number of arterial vascular smooth muscle cells (VSMC) undergo apoptosis at 90 min after the procedure. This apoptotic wave caused significant loss in media cellularity (>90%) over the next 3 h and was accompanied by a marked accumulation of oxidative stress by-products in the vascular wall. Early apoptotic VSMC were rich in p38 mitogen-activated protein kinase (MAPK) and the transcription factor c-Jun and secreted IL-6 and GRO/KC into the milieu as determined using multiplex bead assays. Neointima thickness increased steadily starting on day 3 as a result of pronounced repopulation of the media. A second apoptotic wave that was detected at 14 days after injury affected mostly the neointima and was insufficient to control hyperplasia. Suppression of reactive oxygen species (ROS) production using either the NAD(P)H oxidase inhibitor VAS2870 or pegylated superoxide dismutase (PEG-SOD) significantly decreased the number of apoptotic cells during the first apoptotic wave and showed a trend towards reduction in the neointima-to-media thickness ratio at 30 days post injury. These results indicate that oxidative stress in response to injury induces early-onset apoptosis of VSMC through the activation of redox-sensible MAPK pro-apoptotic pathways. This remodelling process leads to the local accumulation of inflammatory cytokines and repopulation of the media, which ultimately contribute to neointima formation.

Original languageEnglish (US)
Article numbere00227
JournalBioscience Reports
Volume35
Issue number4
DOIs
StatePublished - 2015

Keywords

  • Apoptosis
  • MAPK
  • NAD(P)H oxidase inhibitor
  • Remodelling
  • Superoxide dismutase
  • Vascular injury

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

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