Captopril alleviates doxorubicin-induced cardiac fibrosis and pyroptosis through mechanisms related to the PKN1-Rho/ROCK pathways
- 1Department of Pharmacy, Taizhou Second People’s Hospital, No. 27, Jiankang Road, Jiangyan District, Taizhou, Jiangsu 225300 China
Abstract
Background: Doxorubicin (DOX)-induced cardiac fibrosis and pyroptosis are critical processes contributing to heart failure. This in vitro study examines the protective role of captopril (CTL) in H9c2 cardiomyoblasts, emphasizing the potential involvement of the PKN1-associated Rho/ROCK signaling pathway.
Methods: H9c2 cells were exposed to DOX to induce fibrosis and pyroptosis, followed by CTL treatment. Molecular docking was used to predict CTL-PKN1 interactions. Gene and protein expression were analyzed by RT-qPCR, Western blot, and immunofluorescence. Cell proliferation was assessed using CCK-8, EdU, and flow cytometry assays, while pyroptosis markers were quantified by Western blot.
Results: CTL significantly attenuated DOX-induced fibrosis by downregulating Collagen I, Collagen III, and α-SMA expression. Molecular docking analysis indicated astrong CTL-PKN1 interaction. CTL also suppressed Rho/ROCK pathway activation, whereas PKN1 overexpression reversed CTL’s protective effects, confirming PKN1’s key regulatory role. Additionally, CTL reduced pyroptosis-related proteins, including GSDMD and caspase-1, and decreased cell death.
Conclusion: CTL protects H9c2 cells from DOX-induced cardiac fibrosis and pyroptosis, possibly through modulation of the PKN1-associated Rho/ROCK signaling pathway, highlighting its potential as a therapeutic candidate for cardiac fibrosis-related diseases.
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12872-026-06413-4.
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BibTeX
@article{hua2026captopril,
title = {{Captopril alleviates doxorubicin-induced cardiac fibrosis and pyroptosis through mechanisms related to the PKN1-Rho/ROCK pathways}},
author = {Yiming Hua and Zhimei Huang},
journal = {BMC Cardiovascular Disorders},
year = {2026},
month = aug,
doi = {10.1186/s12872-026-06413-4},
url = {https://doi.org/10.1186/s12872-026-06413-4},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Captopril alleviates doxorubicin-induced cardiac fibrosis and pyroptosis through mechanisms related to the PKN1-Rho/ROCK pathways
AU - Yiming Hua
AU - Zhimei Huang
PY - 2026
DA - 2026/08/07
JO - BMC Cardiovascular Disorders
DO - 10.1186/s12872-026-06413-4
UR - https://doi.org/10.1186/s12872-026-06413-4
AB - Background: Doxorubicin (DOX)-induced cardiac fibrosis and pyroptosis are critical processes contributing to heart failure. This in vitro study examines the protective role of captopril (CTL) in H9c2 cardiomyoblasts, emphasizing the potential involvement of the PKN1-associated Rho/ROCK signaling pathway. Methods: H9c2 cells were exposed to DOX to induce fibrosis and pyroptosis, followed by CTL treatment. Molecular docking was used to predict CTL-PKN1 interactions. Gene and protein expression were analyzed by RT-qPCR, Western blot, and immunofluorescence. Cell proliferation was assessed using CCK-8, EdU, and flow cytometry assays, while pyroptosis markers were quantified by Western blot. Results: CTL significantly attenuated DOX-induced fibrosis by downregulating Collagen I, Collagen III, and α-SMA expression. Molecular docking analysis indicated astrong CTL-PKN1 interaction. CTL also suppressed Rho/ROCK pathway activation, whereas PKN1 overexpression reversed CTL’s protective effects, confirming PKN1’s key regulatory role. Additionally, CTL reduced pyroptosis-related proteins, including GSDMD and caspase-1, and decreased cell death. Conclusion: CTL protects H9c2 cells from DOX-induced cardiac fibrosis and pyroptosis, possibly through modulation of the PKN1-associated Rho/ROCK signaling pathway, highlighting its potential as a therapeutic candidate for cardiac fibrosis-related diseases. Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12872-026-06413-4.
SN - 1471-2261
ER -