The advent of human induced pluripotent stem cells (hiPSCs) and their capacity to be differentiated into beating human cardiomyocytes (CMs) in vitro has revolutionized human disease modelling, genotype-phenotype predictions, and therapeutic testing. Hypertrophic cardiomyopathy (HCM) is a common inherited cardiomyopathy and the leading known cause of sudden cardiac arrest in young adults and athletes. On a molecular level, HCM is often driven by single pathogenic genetic variants, usually in sarcomeric proteins, that can alter the mechanical, electrical, signalling, and transcriptional properties of the cell.
View Article and Find Full Text PDFHypertrophic cardiomyopathy (HCM) is one of the most common heritable cardiovascular diseases and variants of (cardiac troponin T) are linked to increased risk of sudden cardiac arrest despite causing limited hypertrophy. In this study, a variant, R278C, was generated in both human cardiac recombinant/reconstituted thin filaments (hcRTF) and human- induced pluripotent stem cells (hiPSCs) to investigate the mechanisms by which the R278C variant affects cardiomyocytes at the proteomic and functional levels. The results of proteomics analysis showed a significant upregulation of markers of cardiac hypertrophy and remodeling in R278C vs.
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