PD-1 inhibition disrupts collagen homeostasis and aggravates cardiac dysfunction through endothelial-fibroblast crosstalk and EndMT
Our results suggest that PD-1 inhibitor causes ROS accumulation in cardiac ECs, leading to imbalanced collagen distribution (decrease in interstitial collagen and increase in perivascular collagen) in the heart by modulating TCF12/TGF-β1-mediated EC-CF crosstalk and EndMT. NAC supplementation could be an effective clinical strategy to mitigate PD-1 inhibitor-induced imbalanced collagen distribution and cardiac dysfunction.
Authors
- Xiaona Zhao (ORCID: https://orcid.org/0000-0001-6861-148X)
- Zhenzhen Yan (ORCID: https://orcid.org/0000-0001-9356-7425)
- Zejin Zhang (ORCID: https://orcid.org/0000-0002-3309-7027)
- Minghui Wang (ORCID: https://orcid.org/0000-0002-2957-3211)
- Guoqing Liu (ORCID: https://orcid.org/0000-0003-0142-5978)
- Tao Yuan (ORCID: https://orcid.org/0000-0003-1624-6251)
- Lijun Gan (ORCID: https://orcid.org/0000-0002-2694-8022)
- Wei Qin (ORCID: https://orcid.org/0000-0001-6806-9037)
Institutions
- Binzhou Medical University (CN)
- Shandong University of Aeronautics (CN)
- Academic Degrees & Graduate Education (CN)
- Qilu Hospital of Shandong University (CN)
- Shandong First Medical University (CN)
- Jining Medical University (CN)
Publication Details
- Journal
- Frontiers in Pharmacology
- Published
- 2025-03-17
- DOI
- https://doi.org/10.3389/fphar.2025.1549487
- Citations
- 3
- Primary Topic
- Cardiac Fibrosis and Remodeling
- Type
- article
- Field-Weighted Citation Impact
- 4.16