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

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. ...