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Cardiotrophin-1 in hypertensive heart disease

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Abstract

Hypertensive heart disease, here defined by the presence of pathologic left ventricular hypertrophy in the absence of a cause other than arterial hypertension, is characterized by complex changes in myocardial structure including enhanced cardiomyocyte growth and non-cardiomyocyte alterations that induce the remodeling of the myocardium, and ultimately, deteriorate left ventricular function and facilitate the development of heart failure. It is now accepted that a number of pathological processes mediated by mechanical, neurohormonal, and cytokine routes acting on the cardiomyocyte and the non-cardiomyocyte compartments are responsible for myocardial remodeling in the context of arterial hypertension. For instance, cardiotrophin-1 is a cytokine member of the interleukin-6 superfamily, produced by cardiomyocytes and non-cardiomyocytes in situations of biomechanical stress that once secreted interacts with its receptor, the heterodimer formed by gp130 and gp90 (also known as leukemia inhibitory factor receptor beta), activating different signaling pathways leading to cardiomyocyte hypertrophy, as well as myocardial fibrosis. Beyond its potential mechanistic contribution to the development of hypertensive heart disease, cardiotrophin-1 offers the opportunity for a new translational approach to this condition. In fact, recent evidence suggests that cardiotrophin-1 may serve as both a biomarker of left ventricular hypertrophy and dysfunction in hypertensive patients, and a potential target for therapies aimed to prevent and treat hypertensive heart disease beyond blood pressure control.

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Acknowledgments

This study was funded through the agreement between the Foundation for Applied Medical Research (FIMA) and Unión Temporal de Empresas project Centro de Investigación Médica Aplicada (CIMA), the Instituto de Salud Carlos III, Ministry of Science and Innovation, Spain (RECAVA grant RD06/0014/0008, and grant PS09/02234), and the European Union (MEDIA project grant HEALTH-F2-2010-261409, and EU-MASCARA project grant FP7-HEALTH-2011-278249). Arantxa González is recipient of a Ramón y Cajal contract from the Ministry of Science and Innovation, Spain.

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Authors and Affiliations

  1. Área de Ciencias Cardiovasculares, Centro de Investigación Médica Aplicada, Universidad de Navarra, Av. Pío XII 55, 31008, Pamplona, Spain

    Arantxa González, Begoña López, Susana Ravassa, Javier Beaumont, Amaia Zudaire, Idoia Gallego, Cristina Brugnolaro & Javier Díez

  2. Department of Cardiology and Cardiac Surgery, University Clinic, University of Navarra, Pamplona, Spain

    Javier Díez

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  1. Arantxa González
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González, A., López, B., Ravassa, S. et al. Cardiotrophin-1 in hypertensive heart disease. Endocrine 42, 9–17 (2012). https://doi.org/10.1007/s12020-012-9649-4

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