This Article Full Text Full Text (PDF) Data Supplement Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rodríguez-Campos, A. Articles by Badimon, L. Search for Related Content PubMed PubMed Citation Articles by Rodríguez-Campos, A. Articles by Badimon, L. Related Collections Pathophysiology Cell biology/structural biology Smooth muscle proliferation and differentiation Mechanism of atherosclerosis/growth factors

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21:214.)
© 2001 American Heart Association, Inc.

Vascular Biology

Mitogen-Induced p53 Downregulation Precedes Vascular Smooth Muscle Cell Migration From Healthy Tunica Media and Proliferation

Antonio Rodríguez-Campos; Pilar Ruiz-Enríquez; Susanna Faraudo; Lina Badimon

From the Cardiovascular Research Center, IIBB-CSIC, HSCSP, UAB, Barcelona, Spain. Dr Rodríguez-Campos is now at Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain.

Correspondence to Prof Lina Badimon, IIBB-CSIC, Jordi Girona, 18-26, 08034 Barcelona, Spain. E-mail lbmucv{at}cid.csic.es

Abstract—The tumor suppressor protein p53 plays an important role in the cell-cycle G₁ and G₂ checkpoints. In response to DNA damage, p53 can induce the transcription of p21, which inhibits the activation of various G₁ cyclin/cyclin-dependent kinase complexes. It is not known whether p53 plays a role in the initial migration of vascular smooth muscle cells from the arterial tunica media (mVSMCs). In this study, we have investigated whether mVSMC migration from healthy tunica media of young pigs and proliferation are regulated by p53. After 6 hours of incubation in mitogen-rich medium, explanted porcine tunica media tissue showed complete downregulation of p53 protein and p53 mRNA. The blockage of gene activity was not due to DNA methylation at the 5' control region of the gene. The mVSMC outgrowth did not show p53 expression. Mitogen-depletion of cultured p53^-/mVSMCs did not restore p53 expression. Incubation of explanted porcine tunica media tissue in mitogen-deprived medium increased p53 protein content and blocked mVSMC outgrowth from the explant. As in p53-deficient rodent cells, mVSMCs incubated with colcemid overrode the spindle-dependent checkpoint, giving polyploidy and chromosomal pairing. UV-induced DNA damage in mVSMCs incubated with mitogen-free medium induced p53 expression and apoptotic cell death showing DNA nucleosomal laddering. However, UV-irradiated mVSMCs incubated in mitogen-rich medium did not express p53 and did not show cell death. In conclusion, our results demonstrate that early mVSMC migration from the tunica media requires mitogen-induced suppression of p53 that is highly expressed in contractile mVSMCs residing in the healthy vessel wall.

Key Words: p53 • cell proliferation • vascular disease • restenosis • UV irradiation

This article has been cited by other articles:

				C. Dong, W. Yoon, and P. J. Goldschmidt-Clermont DNA Methylation and Atherosclerosis J. Nutr., August 1, 2002; 132(8): 2406S - 2409. [Abstract] [Full Text] [PDF]

				U. Mayr, M. Mayr, C. Li, F. Wernig, H. Dietrich, Y. Hu, and Q. Xu Loss of p53 Accelerates Neointimal Lesions of Vein Bypass Grafts in Mice Circ. Res., February 8, 2002; 90(2): 197 - 204. [Abstract] [Full Text] [PDF]

				U. Mayr, M. Mayr, C. Li, F. Wernig, H. Dietrich, Y. Hu, and Q. Xu Loss of p53 Accelerates Neointimal Lesions of Vein Bypass Grafts in Mice Circ. Res., February 8, 2002; 90(2): 197 - 204. [Abstract] [Full Text] [PDF]