© 2001 American Heart Association, Inc.
Vascular Biology |
Cellular Senescence After Single and Repeated Balloon Catheter Denudations of Rabbit Carotid Arteries
From the Cell Biology Group, Centre for Cardiovascular Biology and Medicine, Department of Medicine (M.F., D.J.K., J.D.E.) and Department of Surgery (S.B.), Royal Free and University College Medical School, University College London, London, UK.
Correspondence to Jorge D. Erusalimsky, PhD, Department of Medicine, University College London, Rayne Institute, Ground Floor, Room G15, 5 University St, London WC1E 6JJ, UK. E-mail j.erusalimsky{at}ucl.ac.uk
Abstract—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 ß-galactosidase (SA-ß-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-ß-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-ß-gal–positive cells were vascular smooth muscle cells, and a minority were endothelial cells. SA-ß-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.
Key Words: endothelial cells • vascular smooth muscle cells • senescence • ß-galactosidase • neointima
This article has been cited by other articles:
 |
|
 |
|
  J. D. Erusalimsky and C. Skene Mechanisms of endothelial senescence Exp Physiol, March 1, 2009; 94(3): 299 - 304. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. D. Erusalimsky Vascular endothelial senescence: from mechanisms to pathophysiology J Appl Physiol, January 1, 2009; 106(1): 326 - 332. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. E. Herbert, Y. Mistry, R. Hastings, T. Poolman, L. Niklason, and B. Williams Angiotensin II-Mediated Oxidative DNA Damage Accelerates Cellular Senescence in Cultured Human Vascular Smooth Muscle Cells via Telomere-Dependent and Independent Pathways Circ. Res., February 1, 2008; 102(2): 201 - 208. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Shi, G. B. Hubbard, R. S. Kushwaha, D. Rainwater, C. A. Thomas III, M. M. Leland, J. L. VandeBerg, and X. L. Wang Endothelial senescence after high-cholesterol, high-fat diet challenge in baboons Am J Physiol Heart Circ Physiol, June 1, 2007; 292(6): H2913 - H2920. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Minamino and I. Komuro Vascular Cell Senescence: Contribution to Atherosclerosis Circ. Res., January 5, 2007; 100(1): 15 - 26. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Hayashi, H. Matsui-Hirai, A. Miyazaki-Akita, A. Fukatsu, J. Funami, Q.-F. Ding, S. Kamalanathan, Y. Hattori, L. J. Ignarro, and A. Iguchi Endothelial cellular senescence is inhibited by nitric oxide: Implications in atherosclerosis associated with menopause and diabetes PNAS, November 7, 2006; 103(45): 17018 - 17023. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Gorenne, M. Kavurma, S. Scott, and M. Bennett Vascular smooth muscle cell senescence in atherosclerosis Cardiovasc Res, October 1, 2006; 72(1): 9 - 17. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Kunieda, T. Minamino, J.-i. Nishi, K. Tateno, T. Oyama, T. Katsuno, H. Miyauchi, M. Orimo, S. Okada, M. Takamura, et al. Angiotensin II Induces Premature Senescence of Vascular Smooth Muscle Cells and Accelerates the Development of Atherosclerosis via a p21-Dependent Pathway Circulation, August 29, 2006; 114(9): 953 - 960. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Chen and M. S. Goligorsky Premature senescence of endothelial cells: Methusaleh's dilemma Am J Physiol Heart Circ Physiol, May 1, 2006; 290(5): H1729 - H1739. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Sampson, M. S. Winterbone, J. C. Hughes, N. Dozio, and D. A. Hughes Monocyte Telomere Shortening and Oxidative DNA Damage in Type 2 Diabetes Diabetes Care, February 1, 2006; 29(2): 283 - 289. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. O. d. Buijs, M. Musters, T. Verrips, J. A. Post, B. Braam, and N. van Riel Mathematical modeling of vascular endothelial layer maintenance: the role of endothelial cell division, progenitor cell homing, and telomere shortening Am J Physiol Heart Circ Physiol, December 1, 2004; 287(6): H2651 - H2658. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. L. Rossi, N. Marziliano, P. A. Merlini, E. Bramucci, U. Canosi, G. Belli, D. Z. Parenti, P. M. Mannucci, and D. Ardissino Different Quantitative Apoptotic Traits in Coronary Atherosclerotic Plaques From Patients With Stable Angina Pectoris and Acute Coronary Syndromes Circulation, September 28, 2004; 110(13): 1767 - 1773. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. J. Kurz, S. Decary, Y. Hong, E. Trivier, A. Akhmedov, and J. D. Erusalimsky Chronic oxidative stress compromises telomere integrity and accelerates the onset of senescence in human endothelial cells J. Cell Sci., May 1, 2004; 117(11): 2417 - 2426. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Haendeler, J. Hoffmann, J. F. Diehl, M. Vasa, I. Spyridopoulos, A. M. Zeiher, and S. Dimmeler Antioxidants Inhibit Nuclear Export of Telomerase Reverse Transcriptase and Delay Replicative Senescence of Endothelial Cells Circ. Res., April 2, 2004; 94(6): 768 - 775. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. T. Weinert and P. S. Timiras Invited Review: Theories of aging J Appl Physiol, October 1, 2003; 95(4): 1706 - 1716. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. J. Kurz, Y. Hong, E. Trivier, H.-L. Huang, S. Decary, G. H. Zang, T. F. Luscher, and J. D. Erusalimsky Fibroblast Growth Factor-2, But Not Vascular Endothelial Growth Factor, Upregulates Telomerase Activity in Human Endothelial Cells Arterioscler. Thromb. Vasc. Biol., May 1, 2003; 23(5): 748 - 754. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. S. Deshpande, B. Qi, Y. C. Park, and K. Irani Constitutive Activation of rac1 Results in Mitochondrial Oxidative Stress and Induces Premature Endothelial Cell Senescence Arterioscler. Thromb. Vasc. Biol., January 1, 2003; 23(1): e1 - 6. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Carlisle, C. A. Rhoads, T. Y. Aw, and L. Harrison Endothelial cells maintain a reduced redox environment even as mitochondrial function declines Am J Physiol Cell Physiol, December 1, 2002; 283(6): C1675 - C1686. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. Erusalimsky, M. Fenton, T. Minamino, H. Miyauchi, T. Yoshida, I. Komuro, Y. Ishida, and H. Yoshida Further In Vivo Evidence That Cellular Senescence Is Implicated in Vascular Pathophysiology * Response Circulation, November 12, 2002; 106 (20): e144 - e144. [Full Text] [PDF]
|
|
|
|
|
|
J. Hoffmann, J. Haendeler, A. Aicher, L. Rossig, M. Vasa, A. M. Zeiher, and S. Dimmeler Aging Enhances the Sensitivity of Endothelial Cells Toward Apoptotic Stimuli: Important Role of Nitric Oxide Circ. Res., October 12, 2001; 89(8): 709 - 715. [Abstract] [Full Text] [PDF]
|
|