And what about epidermal growth factor (EGF) as the bridge between survivin and cardiac remodelling? Raffaella Mormile a, ⁎, Mario De Michele b , Umberto Squarcia c , Federico Quaini d a Division of Pediatric and Neonatology, Moscati Hospital, Aversa, Italy b Division of Cardiology, Moscati Hospital, Aversa, Italy c Pediatric Cardiology, University of Parma, Italy d Department of Internal Medicine and Biomedical Sciences, Section of Internal Medicine, University of Parma, Italy article info Article history: Received 11 January 2011 Accepted 14 January 2011 Available online 18 February 2011 Keywords: Survivin EGF Cardiac remodelling To the editors, Neonates of diabetic mothers are at increased risk for hypertrophic cardiomyopathy whose functional significance is variable. Regardless of severity, cardiac hypertrophy is transient lasting at six months of age as shown by echocardiographic measurements [1]. These findings emphasize the concept that the heart is capable of rapid anatomic remodelling in response to physiologic and pathologic stimuli. However, the molecular mechanism regulating the postnatal regres- sion of hypertrophic cardiomyopathy in infants of diabetic mothers is currently unknown. It has been recently demonstrated that activation of apoptotic cell death involving activation of the MAPK and caspases is correlated with the development and resolution of hypertrophic cardiomyopathy in offspring of diabetic rats [1]. Survivin is a recently characterized member of the inhibitors of apoptosis that probably exerts its action by blunting apoptotic pathways also involving caspases. Survivin is over-expressed during fetal development and in cancer cells but is undetectable in terminally differentiated normal adult tissues [2]. It has been shown that survivin concentrations in cord blood do not reflect the disturbances of feto-placental apoptosis expected in the offspring of diabetic mothers compared to controls [2]. The regression of hypertrophic cardiomyopathy implies that cardio- myocytes survive in spite of the initiation of apoptosis. In this respect, we hypothesized that fetal survivin by balancing cardiomyocyte proliferation and death may drive the reversibility of apoptosis [3]. As a result of this phenomenon the identification of signalling molecules regulating survivin expression in fetal cardiomyocytes, both upstream and downstream, may provide important insights into the machinery driving myocardial regeneration. EGF is regarded as a major component responsible for the effects of the swallowed amniotic fluid on the development of various organs [4]. Human amniotic fluid contains high concentrations of EGF [4]. It is a potent growth factor that plays a key role in fetoplacental development. It is well established that EGF plays an important role in human cardiac differentiation and development including fetal cardiomyocyte pro- liferation [5]. In addition, it has been recently described that EGF regulates survivin stability [6]. Fetal macrosomia, representing one of the complications of gestational diabetes, is not associated with changes in amniotic fluid EGF levels. All together these observations strongly suggest that EGF may be a critical molecule for the up- regulation of prenatal survivin gene expression, promoting the increased resistance to apoptosis with the escape of cardiomyocytes from the point-of-no-return of apoptotic signals. More in-depth studies are needed to better clarify this issue because the interaction between EGF and survivin may be important targets of potential therapeutic interventions aimed at reversing unfavourable cardiac remodelling at any stage of human cardiomyopathies. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [7]. References [1] Reinking BE, Wedemeyer EW, Weiss RB, Segar JL, Scholz TD. Cardiomyopathy in offspring of diabetic rats is associated with activation of the MAPK and apoptotic pathways. Cardiovasc Diabetol 2009;8:43, doi: 10.1186/1475-2840-8-43. [2] Malamitsi-Puchner A, Baka S, Boutsikou M, et al. Cord blood survivin concentra- tions in human full-term normal and complicated pregnancies. In Vivo 2009;23:139–42. [3] Mormile R, De Michele, Squarcia U, Quaini F. Hypertrophic cardiomyopathy in neonates of diabetic mothers: indirect evidence for a model of apoptotic reversibility by survivin? Int J Cardiol 2011 Jan 21;146(2):244–5. [4] Varner MW, Dildy GA, Hunter C, Dudley DJ, Clark SL, Mitchell MD. Amniotic fluid epidermal growth factor levels in normal and abnormal pregnancies. J Soc Gynecol Investig 1996 Jan-Feb;3(1):17–9. [5] Goldman B, Mach A, Wurzel J. Epidermal growth factor promotes a cardiomyoblastic phenotype in human fetal cardiac myocyte. Exp Cell Res 1996 Nov 1;228(2):237–45. [6] Wang H, Gambasova K, Cooper ZA, et al. EGF regulates survivin stability through the RAF-1/ERK pathway in insulin-secreting pancreatic β-cells. Mol Biol 2010;11:66. [7] Shewan LG, Coats AJ. Ethics in the authorship and publishing of scientific article. Int J Cardiol 2010;144:1–2. 0167-5273/$ – see front matter © 2011 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2011.01.049 ⁎ Corresponding author at: Pediatric and Neonatology Unit, Moscati Hospital, Via A. Gramsci, 3, 81031 Aversa, Italy. Tel.: +39 0815001503, +39 3392045468 (Mobile). E-mail address: raffaellamormile@libero.it (R. Mormile). 116 Letters to the Editor