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Differential induction of cellular proliferation, hypertrophy and apoptosis in H9c2 cardiomyocytes by exogenous tissue factor

Collier, M. E W; Seymour, A. M L; Alkistis Frentzou, G.; Collier, Mary E. W.; Ettelaie, Camille; Seymour, Anne-Marie L.


M. E W Collier

A. M L Seymour

G. Alkistis Frentzou

Mary E. W. Collier

Anne-Marie L. Seymour


Recent evidence has shown that prolonged exposure to exogenous tissue factor (TF) can alter the cellular functions of cardiomyocytes resulting in cardiac dysfunction. The effect of TF may arise from local inflammation within or in the vicinity of the heart. The aim of this study was to investigate the effect of TF on cardiomyocyte proliferation and growth. H9c2 rat cardiomyocytes were exposed to a range of concentrations of recombinant TF (rTF) (1.3-52 ng/ml) for up to 10 days and the outcome on cell proliferation and induction of apoptosis measured. At lower concentrations examined (1.3 ng/ml), rTF had a proliferative influence on the H9c2 cells. In contrast, elevated concentrations of rTF (52 ng/ml) induced cellular apoptosis as indicated by increased caspase-3 activity and nuclear localisation of p53. Moreover, incubation with intermediate concentrations of rTF (13 ng/ml) resulted in an initial increase in proliferation but subsequently, led to cellular apoptosis by day 7 of the incubation. In order to determine if these effects induced hypertrophic cell growth, expression of mechano-growth factor (MGF) was analysed. Incubation of cells with rTF resulted in enhanced expression of MGF particularly at the intermediate concentrations of rTF (13 ng/ml) as well as mean cellular transverse diameter. In addition, there was a rapid increase in the expression of atrial natriuretic factor (ANF) in the cells, on incubation with rTF but diminished rapidly when exposed to higher concentrations of rTF. These data indicate that exposure to increasing concentrations of rTF can accelerate the rate of cardiomyocyte turnover which may ultimately lead to depletion of viable cells within the heart. Moreover, at lower concentrations of rTF, the induction of cell proliferation together with hypertrophic markers indicates that rTF may contribute to the induction and progression of cardiac hypertrophy.


Alkistis Frentzou, G., Collier, M. E. W., Ettelaie, C., & Seymour, A. L. (2010). Differential induction of cellular proliferation, hypertrophy and apoptosis in H9c2 cardiomyocytes by exogenous tissue factor. Molecular and Cellular Biochemistry, 345(1-2), 119-130.

Journal Article Type Article
Acceptance Date Jul 29, 2010
Online Publication Date Aug 22, 2010
Publication Date Dec 1, 2010
Print ISSN 0300-8177
Electronic ISSN 1573-4919
Publisher Springer Verlag
Peer Reviewed Peer Reviewed
Volume 345
Issue 1-2
Pages 119-130
Keywords Clinical Biochemistry; Cell Biology; Molecular Biology; General Medicine
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