The role of E2F1 in the development of hypertrophic cardiomyopathy
| Autor: | Wolfram, Julie A, Liner, Anna, Richardson, Sandy L, Zhu, Xiongwei, Smith, Mark A, Hoit, Brian D, Lee, Hyoung-gon |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Male
Mice Knockout endocrine system Cardiotonic Agents Angiotensin II Cell Cycle Isoproterenol Apoptosis Cardiomegaly Mice Transgenic Cardiomyopathy Hypertrophic Mice Gene Expression Regulation cardiovascular system Animals Humans Vasoconstrictor Agents Original Article Myocytes Cardiac RNA Messenger biological phenomena cell phenomena and immunity Atrial Natriuretic Factor E2F1 Transcription Factor Signal Transduction |
| Popis: | 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). Echocardi-ography 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. |
| Databáze: | OpenAIRE |
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