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Int J Clin Exp Pathol 2011;4(5):521-525
Original Ariticle
The role of E2F1 in the development of hypertrophic cardiomyopathy
Julie A. Wolfram, Anna Liner, Sandra L. Richardson, Xiongwei Zhu, Mark A. Smith, Brian D. Hoit , Hyoung-gon Lee
Departments of Pathology and Medicine, Case Western Reserve University, Cleveland, Ohio, USA
Received May 9, 2011; acceptedMay, 2011; Epub May, 2011, published May, 2011
Abstract: The overexpression of the transcription factor, E2F1, induces hypertrophy and apoptosis with cell cycle re-entry in cardiomyocytes in
vitro and in vivo, suggesting that targeting E2F1 may have therapeutic potential. Accordingly, we tested the hypothesis that blocking the
E2F1-mediated signal transduction pathway prevents cardiac hypertrophy by treating E2F1 knockout mice (E2F1-/-) with either isoproterenol
(ISO) or Angiotensin II (ANG). Echocardiography was used to measure left ventricular mass index and myocardial performance index, a
measure of combined systolic and diastolic left ventricular function. In control mice (E2F1+/+) both ISO and ANG treatments induced cardiac
hypertrophy, and impaired ventricular function in ANG treated mice. In contrast to previously published work, E2F1-/- mice also demonstrated a
similar pattern of cardiac hypertrophy and function after either treatment. Atrial natriuretic peptide, a molecular marker of hypertrophy and
necropsy-determined body weight-normalized left ventricle mass were similarly increased in ISO and ANG treated E2F1+/+ and E2F-/- mice,
supporting the echocardiographic data. These data indicate that E2F1 is not necessary for the development of cardiac hypertrophy although
studies using an overexpression approach suggest a causal role of E2F1. The reason for this discrepancy is unclear, although it is possible
that other E2F-family members (e.g., E2F2) may play a compensatory role. In conclusion, our data demonstrate that cardiac hypertrophy can be
induced in an E2F1-independent fashion and suggest that in contrast to previous reports, targeting E2F1 may not be a good therapeutic
approach.(IJCEP1105002)
Keywords: E2F1, Cardiac hypertrophy, isoproterenol, angiotensin II, cardiomyopathy, cell cycle
Full text PDF
Address all correspondence to:
Hyoung-gon Lee, PhD
Department of Pathology
Case Western Reserve University
2103 Cornell Road
Cleveland, Ohio 44106 USA.
Tel: 216-368-6887
Fax: 216-368-8964
E-mail: hyoung-gon.lee@case.edu
Original Ariticle
The role of E2F1 in the development of hypertrophic cardiomyopathy
Julie A. Wolfram, Anna Liner, Sandra L. Richardson, Xiongwei Zhu, Mark A. Smith, Brian D. Hoit , Hyoung-gon Lee
Departments of Pathology and Medicine, Case Western Reserve University, Cleveland, Ohio, USA
Received May 9, 2011; acceptedMay, 2011; Epub May, 2011, published May, 2011
Abstract: The overexpression of the transcription factor, E2F1, induces hypertrophy and apoptosis with cell cycle re-entry in cardiomyocytes in
vitro and in vivo, suggesting that targeting E2F1 may have therapeutic potential. Accordingly, we tested the hypothesis that blocking the
E2F1-mediated signal transduction pathway prevents cardiac hypertrophy by treating E2F1 knockout mice (E2F1-/-) with either isoproterenol
(ISO) or Angiotensin II (ANG). Echocardiography was used to measure left ventricular mass index and myocardial performance index, a
measure of combined systolic and diastolic left ventricular function. In control mice (E2F1+/+) both ISO and ANG treatments induced cardiac
hypertrophy, and impaired ventricular function in ANG treated mice. In contrast to previously published work, E2F1-/- mice also demonstrated a
similar pattern of cardiac hypertrophy and function after either treatment. Atrial natriuretic peptide, a molecular marker of hypertrophy and
necropsy-determined body weight-normalized left ventricle mass were similarly increased in ISO and ANG treated E2F1+/+ and E2F-/- mice,
supporting the echocardiographic data. These data indicate that E2F1 is not necessary for the development of cardiac hypertrophy although
studies using an overexpression approach suggest a causal role of E2F1. The reason for this discrepancy is unclear, although it is possible
that other E2F-family members (e.g., E2F2) may play a compensatory role. In conclusion, our data demonstrate that cardiac hypertrophy can be
induced in an E2F1-independent fashion and suggest that in contrast to previous reports, targeting E2F1 may not be a good therapeutic
approach.(IJCEP1105002)
Keywords: E2F1, Cardiac hypertrophy, isoproterenol, angiotensin II, cardiomyopathy, cell cycle
Full text PDF
Address all correspondence to:
Hyoung-gon Lee, PhD
Department of Pathology
Case Western Reserve University
2103 Cornell Road
Cleveland, Ohio 44106 USA.
Tel: 216-368-6887
Fax: 216-368-8964
E-mail: hyoung-gon.lee@case.edu
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