Language
English
Publication Date
1-11-2025
Journal
npj Regenerative Medicine
DOI
10.1038/s41536-025-00389-z
PMID
39799185
PMCID
PMC11724930
PubMedCentral® Posted Date
1-11-2025
PubMedCentral® Full Text Version
Post-print
Abstract
Cardiomyocytes (CMs) lost during ischemic cardiac injury cannot be replaced due to their limited proliferative capacity. Calcium is an important signal transducer that regulates key cellular processes, but its role in regulating CM proliferation is incompletely understood. Here we show a robust pathway for new calcium signaling-based cardiac regenerative strategies. A drug screen targeting proteins involved in CM calcium cycling in human embryonic stem cell-derived cardiac organoids (hCOs) revealed that only the inhibition of L-Type Calcium Channel (LTCC) induced the CM cell cycle. Furthermore, overexpression of Ras-related associated with Diabetes (RRAD), an endogenous inhibitor of LTCC, induced CM cell cycle activity in vitro, in human cardiac slices, and in vivo. Mechanistically, LTCC inhibition by RRAD or nifedipine induced CM cell cycle by modulating calcineurin activity. Moreover, ectopic expression of RRAD/CDK4/CCND in combination induced CM proliferation in vitro and in vivo, improved cardiac function and reduced scar size post-myocardial infarction.
Keywords
Cell-cycle exit, Calcium signalling
Published Open-Access
yes
Recommended Citation
Devilée, Lynn A C; Salama, Abou Bakr M; Miller, Jessica M; et al., "Pharmacological or Genetic Inhibition of LTCC Promotes Cardiomyocyte Proliferation Through Inhibition of Calcineurin Activity" (2025). Faculty and Staff Publications. 4956.
https://digitalcommons.library.tmc.edu/baylor_docs/4956
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Health Services Research Commons, Medical Cell Biology Commons, Medical Molecular Biology Commons, Medical Specialties Commons, Microbiology Commons