@article{APS11493,
author = {Meng-ying Feng and Yan-song Tang and Su Yao and Hong-jie Zhang and Bi-lin Liu and Rong-rong Huang and Shi-qi Huang and Zhao-hui Ou-yang and Min Yuan and Rui Jiang and Da-chun Xu and Guo-hua Gong and Ke Wei},
title = {Inhibiting L-type calcium channel promotes cardiomyocyte proliferation through activating the canonical Wnt signaling pathway},
journal = {Acta Pharmacologica Sinica},
volume = {47},
number = {4},
year = {2026},
keywords = {},
abstract = {The adult human heart is incapable of regeneration after myocardial infarction (MI) injury. One potential therapeutic strategy is to enhance the proliferation of resident cardiomyocytes (CMs). In this study, we developed a high-content screening assay based on DNA synthesis in human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) to identify small molecules that could promote CM proliferation. In the primary screening, we found that L-type calcium channel (LTCC) blockers induced DNA synthesis of hPSC- CMs. Among the 6 clinically approved calcium channel blockers tested in secondary screening and confirmatory experiments, nimodipine (NM) consistently enhanced CM proliferation both in vitro and in vivo. RNA-Seq analysis revealed that NM activated the canonical Wnt signaling pathway, while inhibiting Wnt signaling blunted the proliferative effect of NM. Lrp5, a co-receptor for Wnt ligands known to interact with LTCC, was found to mediate the effect of NM to promote nuclear localization of β-catenin and CM proliferation. In the MI mouse model established by ligating the left anterior descending coronary artery, administration of NM (10 mg/kg, i.p.) for 7 consecutive days significantly improved cardiac contractile function and enhanced resident CM proliferation, which was attenuated by co-treatment with Wnt inhibitor Wnt-C59 (10 mg/kg, i.p.). Our data suggest that L-type calcium channel blockers that induce CM proliferation may be potentially used in the treatment of MI and heart failure to promote cardiac regeneration.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/11493}
}