A new murine model of stress-induced complex atherosclerotic lesions

Amir H. Najafi, Nima Aghili, Justin U. Tilan, James A. Andrews, Xinzhi Peng, Roberta M. Lassance-Soares, Subeena Sood, Lee O. Alderman, Ken Abe, Lijun Li, Frank D. Kolodgie, Renu Virmani, Zofia Zukowska, Stephen E. Epstein, Mary Susan Burnett

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

The primary purpose of this investigation was to determine whether ApoE-/- mice, when subjected to chronic stress, exhibit lesions characteristic of human vulnerable plaque and, if so, to determine the time course of such changes. We found that the lesions were remarkably similar to human vulnerable plaque, and that the time course of lesion progression raised interesting insights into the process of plaque development. Lard-fed mixed-background ApoE-/- mice exposed to chronic stress develop lesions with large necrotic core, thin fibrous cap and a high degree of inflammation. Neovascularization and intraplaque hemorrhage are observed in over 80% of stressed animals at 20 weeks of age. Previously described models report a prevalence of only 13% for neovascularization observed at a much later time point, between 36 and 60 weeks of age. Thus, our new stress-induced model of advanced atherosclerotic plaque provides an improvement over what is currently available. This model offers a tool to further investigate progression of plaque phenotype to a more vulnerable phenotype in humans. Our findings also suggest a possible use of this stress-induced model to determine whether therapeutic interventions have effects not only on plaque burden, but also, and importantly, on plaque vulnerability.

Original languageEnglish (US)
Pages (from-to)323-331
Number of pages9
JournalDMM Disease Models and Mechanisms
Volume6
Issue number2
DOIs
StatePublished - Mar 2013

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Medicine (miscellaneous)
  • Immunology and Microbiology (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)

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    Najafi, A. H., Aghili, N., Tilan, J. U., Andrews, J. A., Peng, X., Lassance-Soares, R. M., Sood, S., Alderman, L. O., Abe, K., Li, L., Kolodgie, F. D., Virmani, R., Zukowska, Z., Epstein, S. E., & Burnett, M. S. (2013). A new murine model of stress-induced complex atherosclerotic lesions. DMM Disease Models and Mechanisms, 6(2), 323-331. https://doi.org/10.1242/dmm.009977