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 beta-galactosidase activity (SA-beta-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-beta-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.
Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
Sheik J
SJ
Khan
Si
S
Pham
Yunteo
Y
Wei
Dania
D
Mateo
Melissa
M
St-Pierre
Terace M
TM
Fletcher
Roberto I
RI
Vazquez-Padron
D000375:Aging / Q000502:physiology*; D000818:Animals; D001158:Arteries / Q000293:injuries / Q000503:physiopathology; D001808:Blood Vessels / Q000166:cytology / Q000293:injuries / Q000502:physiology*; D002404:Catheterization; D002452:Cell Count; D049109:Cell Proliferation; D002478:Cells, Cultured; D007150:Immunohistochemistry; D008856:Microscopy, Fluorescence; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D017382:Reactive Oxygen Species; D013314:Stress, Mechanical; D001616:beta-Galactosidase / Q000378:metabolism
D017382:Reactive Oxygen Species; D001616:beta-Galactosidase