Pulmonary vascular disease & thromboembolism
ErbB3 Governs Endothelial Dysfunction in Hypoxia-Induced Pulmonary Hypertension
Authors' conclusion
Our study reveals, for the first time, that ErbB3 serves as a novel biomarker and a promising target for the treatment of PH.
Study context
- Population
- Patients with hypoxic PH vs healthy donors; rodents with chronic hypoxia- and Sugen-induced PH; primary human pulmonary artery endothelial and smooth muscle cells
Main finding
As reported in the abstract
- ErbB3 significantly upregulated in serum, lungs, distal pulmonary arteries and pulmonary artery endothelial cells of patients with PH vs healthy donors
- ErbB3 overexpression stimulated hypoxia-induced endothelial cell proliferation, exacerbated pulmonary artery remodeling, elevated RV systolic pressure and promoted RV hypertrophy in murine PH models
- Systemic deletion or endothelial cell-specific knockout of ErbB3 yielded opposite effects
- YB-1 identified as downstream target of ErbB3; ErbB3 induced YB-1 nuclear translocation and promoted hypoxia-inducible factor 1/2α transcription
- Positive ErbB3-periostin-hypoxia-inducible factor 1/2α loop mediates progressive disease development
- MM-121 (anti-ErbB3 monoclonal antibody) had preventive and therapeutic effects against hypoxia-induced PH
Original publication
ErbB3 Governs Endothelial Dysfunction in Hypoxia-Induced Pulmonary Hypertension. Circulation. Published 12 January 2024. doi:10.
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