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Modeling Hypertrophic Cardiomyopathy: Mechanistic Insights and Pharmacological Intervention

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Authors

  • Diogo Mosqueira
  • James Smith
  • Jamie R. Bhagwan
  • Chris Denning

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Abstract

Hypertrophic cardiomyopathy (HCM) is a prevalent and complex cardiovascular disease where cardiac dysfunction often associates with mutations in sarcomeric genes. Various models based on tissue explants, isolated cardiomyocytes, skinned myofibrils, and purified actin/myosin preparations have uncovered disease hallmarks, enabling the development of putative therapeutics, with some reaching clinical trials. Newly developed human pluripotent stem cell (hPSC)-based models could be complementary by overcoming some of the inconsistencies of earlier systems, whilst challenging and/or clarifying previous findings. In this article we compare recent progress in unveiling multiple HCM mechanisms in different models, highlighting similarities and discrepancies. We explore how insight is facilitating the design of new HCM therapeutics, including those that regulate metabolism, contraction and heart rhythm, providing a future perspective for treatment of HCM.

Details

Original languageEnglish
Pages (from-to)775-790
Number of pages16
JournalTrends in Molecular Medicine
Volume25
Issue number9
Early online date17 Jul 2019
DOIs
Publication statusPublished - 1 Sep 2019
Peer-reviewedYes

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