The absence of p53 accelerates atherosclerosis by increasing cell proliferation in vivo (original) (raw)

Nature Medicine volume 5, pages 335–339 (1999)Cite this article

Abstract

The tumor suppressor protein p53 is an essential molecule in cell proliferation and programmed cell death (apoptosis), and has been postulated to play a principal part in the development of atherosclerosis. We have examined the effect of p53 inactivation on atherogenesis in apoE_-knockout mice, an animal model for atherosclerosis1,2. We found that, compared with p53+/+/apoE_ –/– mice, p53 –/– /apoE –/– mice developed considerably accelerated aortic atherosclerosis in the presence of a similar serum cholesterol in response to a high-fat diet. Furthermore, the atherosclerotic lesions in p53 –/– /apoE –/– mice had a significant (~280%) increase in cell proliferation rate and an insignificant (~180%) increase in apoptosis compared with those in p53+/+/apoE –/– mice. Our observations indicate that the role of p53 in atherosclerotic lesion development might be associated with its function in cell replication control, and that p53-independent mechanisms can mediate the apoptotic response in atherosclerosis.

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Acknowledgements

We thank M.E. DeBakey for his interest and support, L. Donehower for his advice, C. Langston for allowing us to use the video imaging system for these studies, E. Zsigmond for assistance with FPLC, M. Majesky for a critical reading of the paper and E. Boerwinkle of The Human Genetics Center of The University of Texas Health Science Center for assistance with the statistical analysis. This work was supported by an NIH grant (HL-51586).

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  1. Natalia V. Guevara
    Present address: Physical Sciences Department, The University of Texas at Brownsville and Texas Southmost College, 80 Fort Brown, Brownsville, Texas, 78520, USA

Authors and Affiliations

  1. Department of Cell Biology and Medicine, Baylor College of Medicine, Houston, 77030, Texas, USA
    Natalia V. Guevara, Ekaterina I. Antonova & Lawrence Chan
  2. Department of Pathology, Baylor College of Medicine, Houston, 77030, Texas, USA
    Han-Seob Kim

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  1. Natalia V. Guevara
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  2. Han-Seob Kim
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  3. Ekaterina I. Antonova
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  4. Lawrence Chan
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Guevara, N., Kim, HS., Antonova, E. et al. The absence of p53 accelerates atherosclerosis by increasing cell proliferation in vivo.Nat Med 5, 335–339 (1999). https://doi.org/10.1038/6585

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