Expression of the cell cycle regulator E2F6 during cardiac development and left ventricular remodeling after myocardial infarction.

The mechanisms underlying the permanent cell cycle arrest of cardiomyocytes shortly after birth are incompletely understood, but likely involve alterations in expression of E2F-responsive genes. E2F6 is a repressor of E2F-responsive genes, and we observed high expression in the heart. To explore its function in cardiac growth, we studied E2F6 expression during normal cardiac development and left ventricular (LV) remodeling after myocardial infarction (MI). LV tissue was collected from rats at different stages of fetal and postnatal development. Expression of E2F6 and of the transcription factors E2F1 and 3 was assessed using real-time PCR and Western blot analysis. MI was induced by coronary artery ligation and LV tissue remote from the scar was collected 3 months post MI. Expression of E2F6 markedly increased during postnatal development while the expression of E2F3 and E2F1 was reduced in adults. Inducing quiescence in fetal cardiomyoblasts caused an upregulation of E2F6 protein (255+25%, P<0.05). After MI, E2F6 mRNA and protein decreased by ∼25% in non-infarcted LV (both P<0.05 versus sham) in an infarct-size dependent manner. Expression of E2F1 and 3 did not change after MI. In conclusion, E2F6 upregulation coincides with cell cycle arrest of cardiomyocytes. Remarkably, E2F6 was downregulated in non-infarcted LV post-MI, suggesting a role in cardiac cell growth and remodeling. Supported by an HSFO grant. [ABSTRACT FROM AUTHOR]