PCSK9 alleviates doxorubicin‑induced pyroptosis of cardiomyocytes.
C, C., J, Z., X, L., S, H., G, L., X, X., C, G., T, Z., J, D., & S, L. (2026). PCSK9 alleviates doxorubicin‑induced pyroptosis of cardiomyocytes.. Molecular medicine reports. https://doi.org/10.3892/mmr.2026.13965
C C, J Z, X L, S H, G L, X X, et al. PCSK9 alleviates doxorubicin‑induced pyroptosis of cardiomyocytes.. Molecular medicine reports. 2026; doi: 10.3892/mmr.2026.13965
C C, J Z, X L, et al. PCSK9 alleviates doxorubicin‑induced pyroptosis of cardiomyocytes.[J]. Molecular medicine reports. 2026. DOI: 10.3892/mmr.2026.13965.
@article{c2026,
author = {Cui C and Zhao J and Li X and Huang S and Liu G and Xu X and Guo C and Zhao T and Du J and Li S},
title = {PCSK9 alleviates doxorubicin‑induced pyroptosis of cardiomyocytes.},
journal = {Molecular medicine reports},
year = {2026},
doi = {10.3892/mmr.2026.13965},
note = {PMID: 42464669},
}
TY - JOUR AU - Cui C AU - Zhao J AU - Li X AU - Huang S AU - Liu G AU - Xu X AU - Guo C AU - Zhao T AU - Du J AU - Li S TI - PCSK9 alleviates doxorubicin‑induced pyroptosis of cardiomyocytes. T2 - Molecular medicine reports PY - 2026 DO - 10.3892/mmr.2026.13965 AN - PMID:42464669 ER -
Prolonged survival of patients with cancer has increased the need to address chemotherapy‑related cardiovascular complications. Doxorubicin (DOX), a widely used anthracycline, is associated with dose‑dependent cardiotoxicity, known as DOX‑induced cardiotoxicity (DIC), which limits its clinical utility. DOX triggers cardiomyocyte pyroptosis via the NLRP3/caspase‑1/gasdermin D pathway, a potential underlying mechanism of DIC. Proprotein convertase subtilisin/kexin type 9 (PCSK9), a key regulator of lipid metabolism and inflammation, has been implicated in NLRP3 inflammasome activation and the progression of cardiovascular diseases; however, its role in DIC remains unclear. The present study demonstrated that DOX downregulates PCSK9 expression in cardiomyocytes in a dose‑dependent manner. Through proteomic analysis and PCSK9 knockout cell and mouse models, it was found that the deletion of PCSK9 exacerbated DOX‑induced pyroptosis and cardiac dysfunction. These results revealed the protective effect of PCSK9 in DOX‑mediated cardiotoxicity and indicated that PCSK9 regulation may provide a new cardioprotective strategy for patients receiving anthracycline chemotherapy.