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Transcriptional Network Analysis for the Regulation of Left Ventricular Hypertrophy and Microvascular Remodeling

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Abstract

Hypertension and cardiomyopathies share maladaptive changes of cardiac morphology, eventually leading to heart failure. These include left ventricular hypertrophy (LVH), myocardial fibrosis, and structural remodeling of coronary microcirculation, which is the morphologic hallmark of coronary microvascular dysfunction. To pinpoint the complex molecular mechanisms and pathways underlying LVH-associated cardiac remodeling independent of blood pressure effects, we employed gene network approaches to the rat heart. We used the Spontaneously Hypertensive Rat model showing many features of human hypertensive cardiomyopathy, for which we collected histological and histomorphometric data of the heart and coronary vasculature, and genome-wide cardiac gene expression. Here, we provide a large catalogue of gene co-expression networks in the heart that are significantly associated with quantitative variation in LVH, microvascular remodeling, and fibrosis-related traits. Many of these networks were significantly conserved to human idiopathic and/or ischemic cardiomyopathy patients, suggesting a potential role for these co-expressed genes in human heart disease.

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Acknowledgments

We acknowledge funding from the European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement no. HEALTH-F4-2010-241504 (EURATRANS) (E.P.), the Medical Research Council (E.P.), and the British Heart Foundation (PhD Studentship grant FS/11/25/28740; E.P. and A.M.M.).

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Authors and Affiliations

  1. Medical Research Council (MRC) Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Imperial Centre for Translational and Experimental Medicine (ICTEM) Building, Du Cane Road, London, W12 0NN, UK

    Aida Moreno-Moral & Enrico Petretto

  2. Department of Radiology, Oncology and Pathology, Sapienza University of Rome, Rome, Italy

    Massimiliano Mancini & Giulia D’Amati

  3. San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy

    Paolo Camici

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  1. Aida Moreno-Moral
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  2. Massimiliano Mancini
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  3. Giulia D’Amati
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  4. Paolo Camici
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  5. Enrico Petretto
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Correspondence to Enrico Petretto.

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Associate Editor Enrique Lara-Pezzi oversaw the review of this article

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Moreno-Moral, A., Mancini, M., D’Amati, G. et al. Transcriptional Network Analysis for the Regulation of Left Ventricular Hypertrophy and Microvascular Remodeling. J. of Cardiovasc. Trans. Res. 6, 931–944 (2013). https://doi.org/10.1007/s12265-013-9504-x

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