AGE

, Volume 28, Issue 1, pp 85–91 | Cite as

Sequestration of p27 within the cytoplasm of cardiac myocytes in chronic ischemic heart disease: pathogenic implications for ischemic cardiomyopathy

  • Mark A. Smith
  • Xiongwei Zhu
  • Hyoung-gon Lee
  • Peggy L. R. Harris
  • Anne E. Fortino
  • George Perry
  • Rudy J. Castellani
Original Paper
  • 32 Downloads

Abstract

A number of recent studies have suggested that cardiac myocytes, previously considered post-mitotic, re-enter the cell cycle and possess the ability to proliferate with certain pathogenic stimuli. To study this further, we examined cellular proliferation in myocardial tissue from subjects with chronic ischemic heart disease-associated myocardial infarction and subsequent congestive heart failure. We found striking increases in cytoplasmic phospho-p27, a well-known mitotic regulator, compared to controls by both immunocytochemical and immunoblot analyses. However, we found no evidence for cardiac myocyte proliferation in either disease or control subjects using both mitotic counting (no mitotic figures were observed) and Ki-67 immunocytochemistry, which demonstrated a 0% proliferation index. That increased cytoplasmic phospho-p27 is not accompanied by division prompts us to speculate that ectopic cell cycle activation occurs in the face of minimal to absent myocyte proliferation per se. Based on these findings, and the parallel findings in post-mitotic neurons in neurodegenerative disease, we suggest that cell-cycle activation in ischemic heart disease is a deleterious event that perpetuates disease pathogenesis culminating in myocardial failure.

Key words

binucleation cell cycle immunocytochemistry Ki-67 mitosis myocardial infarct myocyte p27 proliferation 

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Copyright information

© Springer Science + Business Media B.V. 2006

Authors and Affiliations

  • Mark A. Smith
    • 1
  • Xiongwei Zhu
    • 1
  • Hyoung-gon Lee
    • 1
  • Peggy L. R. Harris
    • 1
  • Anne E. Fortino
    • 2
  • George Perry
    • 1
  • Rudy J. Castellani
    • 3
  1. 1.Department of PathologyCase Western Reserve UniversityClevelandUSA
  2. 2.Division of NeuropathologyMichigan State UniversityEast LansingUSA
  3. 3.Department of PathologyUniversity of MarylandBaltimoreUSA

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