Cellular senescence after single and repeated balloon catheter denudations of rabbit carotid arteries.
The hypothesis that increased cellular proliferation in the vasculature may lead to replicative senescence has been tested in a model of neointima formation. We have used a biomarker of replicative senescence, senescence-associated beta-galactosidase (SA-beta-gal), to detect senescence in rabbit carotid arteries subjected to single and double balloon denudations. We found an accumulation of senescent cells in the neointima and media of all injured vessels, in contrast to the near absence of such cells in control vessels. The relative area occupied by SA-beta-gal-positive cells was higher in vessels subjected to double denudation than in those subjected to single denudation, both in the neointima (0.99% versus 0.06%, respectively; P:<0.001) and in the media (0.11% versus 0.01%, respectively; P:<0.02). The majority of SA-beta-gal-positive cells were vascular smooth muscle cells, and a minority were endothelial cells. SA-beta-gal-positive cells showed no evidence of apoptosis by use of terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling. Our results indicate that the proliferative response that follows intraluminal injury to the artery leads to the emergence of senescent endothelial and smooth muscle cells. The demonstration that vascular cell senescence can occur in vivo suggests that this process may be involved in cardiovascular pathologies that have a proliferative component.
Fenton
M
M
Cell Biology Group, Centre for Cardiovascular Biology and Medicine, Department of Medicine, Royal Free and University College Medical School, University College London, London, UK.
Barker
S
S
Kurz
D J
DJ
Erusalimsky
J D
JD
D000800:Angioplasty, Balloon / Q000009:adverse effects*; D000818:Animals; D015415:Biomarkers; D002339:Carotid Arteries / Q000473:pathology*; D020212:Carotid Artery Injuries / Q000209:etiology / Q000473:pathology*; D016922:Cellular Senescence / Q000235:genetics / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000293:injuries; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000293:injuries; D011817:Rabbits; D001616:beta-Galactosidase / Q000378:metabolism
D015415:Biomarkers; D001616:beta-Galactosidase