Inhibition of apoptotic signaling and neointimal hyperplasia by tempol and nitric oxide synthase following vascular injury.

Published

Journal Article

OBJECTIVES: We hypothesized that redox-mediated apoptosis of medial smooth muscle cells (SMC) during the acute phase of vascular injury contributes to the pathophysiology of vascular disease. METHODS: Apoptosis of medial SMC (1-14 days following balloon injury) was identified in rat carotid arteries by in situ DNA labeling. NADPH-derived superoxide and expression of Bcl-xL, Bax, caspase-3 and caspase-9 were assessed. The antioxidant tempol was administered in drinking water throughout the experimental period, and local adenoviral-mediated gene transfer of eNOS was performed prior to vascular injury. RESULTS: Balloon injury increased NADPH-dependent superoxide production, medial SMC apoptosis, Bax-positive medial SMC index, Bax/Bcl-xL ratio, and caspase-3 and caspase-9 expression in the injured arteries. Treatment with tempol or eNOS gene transfer decreased superoxide levels and medial SMC apoptosis, with a concomitant increase in medial SMC density. Inhibition of superoxide was associated with a decreased Bax/Bcl-xL ratio, and caspase-3 and -9 expression. Tempol treatment and eNOS gene therapy significantly reduced neointima formation. CONCLUSION: Vascular generation of reactive oxygen species participates in Bax activation and medial SMC apoptosis. These effects likely contribute to the shedding of cell-cell adhesion molecules and promote medial SMC migration and proliferation responsible for neointimal hyperplasia.

Full Text

Duke Authors

Cited Authors

  • Jagadeesha, DK; Miller, FJ; Bhalla, RC

Published Date

  • 2009

Published In

Volume / Issue

  • 46 / 2

Start / End Page

  • 109 - 118

PubMed ID

  • 18714161

Pubmed Central ID

  • 18714161

Electronic International Standard Serial Number (EISSN)

  • 1423-0135

Digital Object Identifier (DOI)

  • 10.1159/000151444

Language

  • eng

Conference Location

  • Switzerland