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Sarcomere Gene Mutations in Hypertrophy and Heart Failure

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Abstract

Despite considerable progress in identifying and modifying risk factors that cause cardiovascular disease, heart failure has emerged as an important medical and socioeconomic problem. Hypertrophic remodeling, a common response to many cardiovascular disorders, increases the risk of heart failure. Discovery of the genetic basis of hypertrophic cardiomyopathy has allowed consideration of whether these genes also contribute to pathologic remodeling that occurs in the context of common acquired cardiovascular disorders. Evidence supporting a shared etiology has emerged from the recent identification of sarcomere protein mutations and sequence variants in community-based populations with hypertrophy and heart failure. These findings imply that harnessing genetic testing for hypertrophic mutations may help define patients at risk for heart failure. In the future, mechanistic insights into hypertrophic remodeling, combined with strategies to prevent this pathology, are expected to reduce the burden of heart failure.

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Acknowledgements

This work was supported, in part, by grants from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (H.M. and R.N.), the TAKEDA Science Foundation (H.M.), the National Institutes of Health (J.G.S. and C.E.S.), the Leducq Foundation (J.G.S. and C.E.S.), and the Howard Hughes Medical Institute (C.E.S.).

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Authors and Affiliations

  1. Department of Translational Research for Healthcare and Clinical Science, Graduate School of Medicine, University of Tokyo, Tokyo, Japan

    Hiroyuki Morita

  2. Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan

    Ryozo Nagai

  3. Department of Genetics, Harvard Medical School, NRB Room 256, 77 Avenue Louis Pasteur, Boston, MA, 02115, USA

    J. G. Seidman & Christine E. Seidman

  4. Cardiovascular Division, Brigham and Women’s Hospital and Howard Hughes Medical Institute, Boston, MA, USA

    Christine E. Seidman

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  1. Hiroyuki Morita
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  2. Ryozo Nagai
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  4. Christine E. Seidman
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Correspondence to Christine E. Seidman.

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Morita, H., Nagai, R., Seidman, J.G. et al. Sarcomere Gene Mutations in Hypertrophy and Heart Failure. J. of Cardiovasc. Trans. Res. 3, 297–303 (2010). https://doi.org/10.1007/s12265-010-9188-4

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