Key result
TCAP-knockdown cuts iPSC-cardiomyocyte contraction velocity ~43% vs wild-type and provokes aberrant Ca2+-waves.
Why the study?
Dilated cardiomyopathy is a leading cause of heart failure linked to multiple genes, and at least six TCAP variants have been identified in DCM patients, prompting investigation into the role of TCAP in cardiac function.
TCAP knockdown in human iPSC-derived cardiomyocytes impairs contractility and calcium handling, providing mechanistic insight into its role in dilated cardiomyopathy.
TCAP knockdown impairs iPSC-cardiomyocyte function; hypothesis-generating for its role in cardiomyopathy, requiring in vivo validation before clinical consideration.
Objectives Dilated cardiomyopathy (DCM) is one of the leading causes of heart failure. To date, 48 genes are known to be associated with DCM. Telethonin, encoded by the TCAP gene, is a Z-disk protein that composes cytoskeletal structures and facilitates various signaling pathways in cardiomyocytes. At least, six TCAP variants have been found in patients with DCM. We sought to investigate the role of TCAP in cardiac function using TCAP-knockdown (KD) iPS cell (iPSC)-induced cardiomyocytes (CMs).
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Handoh et al. (2025) studied Dilated cardiomyopathy (in vitro model) (n=78). TCAP-knockdown via CRISPR-Cas9 vs. Wild-type iPSC-induced cardiomyocytes was evaluated on Contraction velocity (µm/s) (p=<0.001). TCAP-knockdown in human iPS cell-induced cardiomyocytes significantly decreased contraction velocity compared to wild-type cells (29.11 vs 51.28 µm/s, p<0.001) and provoked aberrant Ca2+-waves.
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