期刊
TRENDS IN MOLECULAR MEDICINE
卷 25, 期 9, 页码 775-790出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.molmed.2019.06.005
关键词
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资金
- British Heart Foundation (BHF) [SP/15/9/31605, PG/14/59/31000, RG/14/1/30588, RM/13/30157, P47352/CRM]
- Britain Israel Research and Academic Exchange Partnership (BIRAX) [04BX14CDLG]
- Medical Research Council (MRC) [MR/M017354/1]
- Engineering and Physical Sciences Research Council (EPSRC) [DM's Doctoral Prize Research Fellowship]
- National Centre for the Replacement, Refinement, and Reduction of Animals in Research (NC3Rs) [CRACK-IT:35911-259146, NC/K000225/1, NC/S001808/1]
- Heart Research UK
- German Research Foundation [DFG-Es-88/12-1, HA3423/5-1]
- European Research Council [ERC-AG-IndivuHeart]
- European Commission [FP7-Biodesign]
- German Centre for Cardiovascular Research (DZHK)
- German Ministry of Education and Research
- Freie und Hansestadt Hamburg
- MRC [MR/L012618/1, MR/M017354/1] Funding Source: UKRI
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.
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