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¹ Department of Medicine, University of Lausanne Medical School, CH-1011 Lausanne, Switzerland
² Swiss Institute for Experimental Cancer Research, Swiss Institute of Technology, CH-1066 Epalinges, Switzerland

CORRESPONDENCE Thierry Pedrazzini: thierry.pedrazzini{at}chuv.ch

In the damaged heart, cardiac adaptation relies primarily on cardiomyocyte hypertrophy. The recent discovery of cardiac stem cells in the postnatal heart, however, suggests that these cells could participate in the response to stress via their capacity to regenerate cardiac tissues. Using models of cardiac hypertrophy and failure, we demonstrate that components of the Notch pathway are up-regulated in the hypertrophic heart. The Notch pathway is an evolutionarily conserved cell-to-cell communication system, which is crucial in many developmental processes. Notch also plays key roles in the regenerative capacity of self-renewing organs. In the heart, Notch1 signaling takes place in cardiomyocytes and in mesenchymal cardiac precursors and is activated secondary to stimulated Jagged1 expression on the surface of cardiomyocytes. Using mice lacking Notch1 expression specifically in the heart, we show that the Notch1 pathway controls pathophysiological cardiac remodeling. In the absence of Notch1, cardiac hypertrophy is exacerbated, fibrosis develops, function is altered, and the mortality rate increases. Therefore, in cardiomyocytes, Notch controls maturation, limits the extent of the hypertrophic response, and may thereby contribute to cell survival. In cardiac precursors, Notch prevents cardiogenic differentiation, favors proliferation, and may facilitate the expansion of a transient amplifying cell compartment.

A. Croquelois, A.A. Domenighetti, and M. Nemir contributed equally to this paper.

© 2008 Croquelois et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

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This article has been cited by other articles:

• Rochais, F., Mesbah, K., Kelly, R. G. (2009). Signaling Pathways Controlling Second Heart Field Development. Circ. Res. 104: 933-942 [Abstract] [Full Text]  
• Croquelois, A., Domenighetti, A. A., Nemir, M., Lepore, M., Rosenblatt-Velin, N., Radtke, F., Pedrazzini, T. (2008). Control of the adaptive response of the heart to stress via the Notch1 receptor pathway. JCB 183: i16-i16 [Full Text]  

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