Molecular Medicine

, Volume 18, Issue 6, pp 938–947 | Cite as

Signaling to Cardiac Hypertrophy: Insights from Human and Mouse RASopathies

  • Valentina Sala
  • Simona Gallo
  • Christian Leo
  • Stefano Gatti
  • Bruce D Gelb
  • Tiziana Crepaldi
Review Article


Cardiac hypertrophy is the heart’s response to a variety of extrinsic and intrinsic stimuli, some of which might finally lead up to a maladaptive state. An integral part of the pathogenesis of the hypertrophic cardiomyopathy disease (HCM) is the activation of the rat sarcoma (RAS)/RAF/MEK (mitogen-activated protein kinase kinase)/MAPK (mitogen-activated protein kinase) cascade. Therefore, the molecular signaling involving RAS has been the subject of intense research efforts, particularly after the identification of the RASopathies. These constitute a class of developmental disorders caused by germline mutations affecting proteins contributing to the RAS pathway. Among other phenotypic features, a subset of these syndromes is characterized by HCM, prompting researchers and clinicians to delve into the chief signaling constituents of cardiac hypertrophy. In this review, we summarize current advances in the knowledge of the molecular signaling events involved in the pathogenesis of cardiac hypertrophy through work completed on patients and on genetically manipulated animals with HCM and RASopathies. Important insights are drawn from the recognition of parallels between cardiac hypertrophy and cancer. Future research promises to further elucidate the complex molecular interactions responsible for cardiac hypertrophy, possibly pointing the way for the identification of new specific targets for the treatment of HCM.



We kindly acknowledge the constant support of the Association Francaise contre les Myopathies (AFM) and the Seventh Framework Programme. V Sala was a Fellow of Università Italo Francese in 2011 (UIF, Cap. III Progetto Vinci 2008). The fellowships of V Sala and C Leo were granted by the FP7-2010-ICT-GC „EM-SAFETY“ project no. 265772. We gratefully thank GB Ferrero for helpful discussion.


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Authors and Affiliations

  • Valentina Sala
    • 1
  • Simona Gallo
    • 1
  • Christian Leo
    • 1
  • Stefano Gatti
    • 1
  • Bruce D Gelb
    • 2
  • Tiziana Crepaldi
    • 1
  1. 1.Department of Anatomy, Pharmacology and Forensic MedicineUniversity of TurinTurinItaly
  2. 2.Child Health and Development InstituteMount Sinai School of MedicineNew YorkUSA

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