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p53 functions in endothelial cells to prevent radiation-induced myocardial injury in mice.

Publication ,  Journal Article
Lee, C-L; Moding, EJ; Cuneo, KC; Li, Y; Sullivan, JM; Mao, L; Washington, I; Jeffords, LB; Rodrigues, RC; Ma, Y; Das, S; Kontos, CD; Kim, Y ...
Published in: Sci Signal
July 24, 2012

Radiation therapy, which is used for the treatment of some cancers, can cause delayed heart damage. In the heart, p53 influences myocardial injury that occurs after multiple types of stress. Here, we demonstrated that p53 functioned in endothelial cells to protect mice from myocardial injury after whole-heart irradiation. Mice with an endothelial cell-specific deletion of p53 succumbed to heart failure after whole-heart irradiation as a result of myocardial necrosis, systolic dysfunction, and cardiac hypertrophy. Moreover, the onset of cardiac dysfunction was preceded by alterations in myocardial vascular permeability and density, which resulted in cardiac ischemia and myocardial hypoxia. Mechanistic studies with primary cardiac endothelial cells irradiated in vitro indicated that p53 signaling caused mitotic arrest and protected cardiac endothelial cells from cell death resulting from abnormal mitosis or mitotic catastrophe. Furthermore, mice lacking the cyclin-dependent kinase inhibitor p21, which is a transcriptional target of p53, were also sensitized to myocardial injury after whole-heart irradiation. Together, our results demonstrate that the p53-p21 axis functions to prevent radiation-induced myocardial injury in mice.

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Published In

Sci Signal

DOI

EISSN

1937-9145

Publication Date

July 24, 2012

Volume

5

Issue

234

Start / End Page

ra52

Location

United States

Related Subject Headings

  • p21-Activated Kinases
  • Tumor Suppressor Protein p53
  • Systole
  • Receptor, TIE-2
  • Radiotherapy
  • Radiation Injuries, Experimental
  • Necrosis
  • Myocardium
  • Mice, Transgenic
  • Mice
 

Citation

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Lee, C.-L., Moding, E. J., Cuneo, K. C., Li, Y., Sullivan, J. M., Mao, L., … Kirsch, D. G. (2012). p53 functions in endothelial cells to prevent radiation-induced myocardial injury in mice. Sci Signal, 5(234), ra52. https://doi.org/10.1126/scisignal.2002918
Lee, Chang-Lung, Everett J. Moding, Kyle C. Cuneo, Yifan Li, Julie M. Sullivan, Lan Mao, Iman Washington, et al. “p53 functions in endothelial cells to prevent radiation-induced myocardial injury in mice.Sci Signal 5, no. 234 (July 24, 2012): ra52. https://doi.org/10.1126/scisignal.2002918.
Lee C-L, Moding EJ, Cuneo KC, Li Y, Sullivan JM, Mao L, et al. p53 functions in endothelial cells to prevent radiation-induced myocardial injury in mice. Sci Signal. 2012 Jul 24;5(234):ra52.
Lee, Chang-Lung, et al. “p53 functions in endothelial cells to prevent radiation-induced myocardial injury in mice.Sci Signal, vol. 5, no. 234, July 2012, p. ra52. Pubmed, doi:10.1126/scisignal.2002918.
Lee C-L, Moding EJ, Cuneo KC, Li Y, Sullivan JM, Mao L, Washington I, Jeffords LB, Rodrigues RC, Ma Y, Das S, Kontos CD, Kim Y, Rockman HA, Kirsch DG. p53 functions in endothelial cells to prevent radiation-induced myocardial injury in mice. Sci Signal. 2012 Jul 24;5(234):ra52.

Published In

Sci Signal

DOI

EISSN

1937-9145

Publication Date

July 24, 2012

Volume

5

Issue

234

Start / End Page

ra52

Location

United States

Related Subject Headings

  • p21-Activated Kinases
  • Tumor Suppressor Protein p53
  • Systole
  • Receptor, TIE-2
  • Radiotherapy
  • Radiation Injuries, Experimental
  • Necrosis
  • Myocardium
  • Mice, Transgenic
  • Mice