title: Sequestration of p27 within the cytoplasm of cardiac myocytes in chronic ischemic heart disease: pathogenic implications for ischemic cardiomyopathy.
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.
authors.affiliation: Department of Pathology, Case Western Reserve University, 2103 Cornell Road, Cleveland, OH 44106 USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Smith
authors.forename: Xiongwei
authors.initials: X
authors.lastname: Zhu
authors.forename: Hyoung-Gon
authors.initials: HG
authors.lastname: Lee
authors.forename: Peggy L R
authors.initials: PL
authors.lastname: Harris
authors.forename: Anne E
authors.initials: AE
authors.lastname: Fortino
authors.forename: George
authors.initials: G
authors.lastname: Perry
authors.forename: Rudy J
authors.initials: RJ
authors.lastname: Castellani
keywords: Ki-67; binucleation; cell cycle; immunocytochemistry; mitosis; myocardial infarct; myocyte; p27; proliferation