© 2002 by European Society of Cardiology
Copyright © 2002, European Society of Cardiology
Direct evidence for the importance of p130 in injury response and arterial remodeling following carotid artery ligation
aKrannert Institute of Cardiology and Indiana Center for Vascular Biology and Medicine, Indiana University Medical Center, Indianapolis, IN 46202, USA
bInstitute for Arteriosclerosis Research and Department of Medicine, Cardiology/Angiology, University of Münster, Münster, Germany
sinderm{at}uni-muenster.de
* Corresponding author. Institute for Arteriosclerosis Research and Department of Medicine, Cardiology/Angiology, University of Münster, Domagkstrasse 3, 48149 Münster, Germany. Tel.: +49-251-8355-326; fax: +49-251-8352-980
Objective: Remodeling of arterial morphology in atherosclerosis, hypertension, and restenosis following angioplasty involves controlled alterations in total vascular circumference which critically modulate sequelae of changes in vessel wall mass. Despite the clinical relevance of this process little is known about the pathophysiology, especially the correlation between smooth muscle cell proliferation and remodeling. Methods: Carotid artery ligation was applied to mice with targeted disruption of the p130 gene (p130 –/–). Mice were allowed to recover for 3 weeks after ligation and then perfusion fixed for histologic and morphometric analysis. Results: P130 –/– mice were indistinguishable from control littermates concerning size and weight. As for the aorta, carotid arteries and femoral arteries, no significant differences were found between the groups with regard to vessel size and cellular density of the vessel wall of non-instrumented vessels. In contrast, following carotid artery ligation we found p130 –/– mice (n=8) to develop a significant increase in vessel wall area compared to controls (n=9). Mean values ranged from 3.07x10–2±0.20x10–2–3.56x10–2±0.62x10–2 mm2 for p130 –/– mice versus 2.26x10–2±0.13x10–2–2.57x10–2±0.26x10–2 mm2 for controls (p=0.02) along the lesion studied. This increase in vessel wall area was primarily due to a sevenfold mean increase in neointima in p130 –/– mice yielding mean values of 0.43±0.18 – 1.19±0.70x10–2 mm2. Remarkably, despite vessel wall increase, the lumen area was not statistically different for both groups. Conclusions: The data indicate that the loss of the cell cycle inhibitor p130 leads to an enhanced injury response, implicating a central role of p130 in cell cycle control during response to injury in the vessel wall. The enhanced injury response in the context of p130 –/– preserves the ability to perform perfect remodeling, thus the remodeling capacity is preserved even in the context of this injury model.
KEYWORDS Arteries; Gene expression; Remodeling; Restenosis; Smooth muscle
1 New address: Eli Lilly Company, Indianapolis, IN 46254, USA.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  F. Gizard, T. Nomiyama, Y. Zhao, H. M. Findeisen, E. B. Heywood, K. L. Jones, B. Staels, and D. Bruemmer The PPAR{alpha}/p16INK4a Pathway Inhibits Vascular Smooth Muscle Cell Proliferation by Repressing Cell Cycle-Dependent Telomerase Activation Circ. Res., November 7, 2008; 103(10): 1155 - 1163. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-H. Du, Y.-Y. Guan, N. J. Alp, K. M. Channon, and A. F. Chen Endothelium-Specific GTP Cyclohydrolase I Overexpression Attenuates Blood Pressure Progression in Salt-Sensitive Low-Renin Hypertension Circulation, February 26, 2008; 117(8): 1045 - 1054. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Bakay, Z. Wang, G. Melcon, L. Schiltz, J. Xuan, P. Zhao, V. Sartorelli, J. Seo, E. Pegoraro, C. Angelini, et al. Nuclear envelope dystrophies show a transcriptional fingerprint suggesting disruption of Rb-MyoD pathways in muscle regeneration Brain, April 1, 2006; 129(4): 996 - 1013. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. R. Sindermann, C. Kobbert, A. Skaletz-Rorowski, G. Breithardt, G. Plenz, and K. L. March Vascular injury response in mice is dependent on genetic background Am J Physiol Heart Circ Physiol, March 1, 2006; 290(3): H1307 - H1310. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. L. Myers and L. Liaw Improved Analysis of the Vascular Response to Arterial Ligation Using a Multivariate Approach Am. J. Pathol., January 1, 2004; 164(1): 43 - 48. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. A. Korshunov and B. C. Berk Flow-Induced Vascular Remodeling in the Mouse: A Model for Carotid Intima-Media Thickening Arterioscler Thromb Vasc Biol, December 1, 2003; 23(12): 2185 - 2191. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. R. Sindermann, C. Kobbert, F. Bauer, A. Skaletz-Rorowski, H. Hohage, G. Plenz, G. Breithardt, and K. L. March Vascular ligation response is independent of p107: stressing the role of the related p130 Am J Physiol Heart Circ Physiol, July 11, 2003; 285(2): H915 - H918. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. R. Sindermann, P. Babij, J. C. Klink, C. Kobbert, G. Plenz, J. Ebbing, L. Fan, and K. L. March Smooth muscle-specific expression of SV40 large TAg induces SMC proliferation causing adaptive arterial remodeling Am J Physiol Heart Circ Physiol, December 1, 2002; 283(6): H2714 - H2724. [Abstract] [Full Text] [PDF]
|
|