Endothelial protein C receptor promotes retinal neovascularization through heme catabolism
Abstract Pathological retinal neovascularization (RNV) is one of the leading causes of blindness worldwide; however, its underlying mechanism remains unclear. Here, we found that the expression of endothelial protein C receptor (Epcr) was increased during RNV, and its ligand was elevated in the seru...
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| Format: | Article |
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Nature Portfolio
2025-02-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56810-0 |
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| author | Hongyuan Song Qing Li Xiao Gui Ziyu Fang Wen Zhou Mengzhu Wang Yuxin Jiang Ajun Geng Xi Shen Yongxuan Liu Haorui Zhang Zheng Nie Lin Zhang Huimin Zhu Feng Zhang Xuri Li Fanyan Luo Hongjian Zhang Wei Shen Xiaodong Sun |
| author_facet | Hongyuan Song Qing Li Xiao Gui Ziyu Fang Wen Zhou Mengzhu Wang Yuxin Jiang Ajun Geng Xi Shen Yongxuan Liu Haorui Zhang Zheng Nie Lin Zhang Huimin Zhu Feng Zhang Xuri Li Fanyan Luo Hongjian Zhang Wei Shen Xiaodong Sun |
| author_sort | Hongyuan Song |
| collection | DOAJ |
| description | Abstract Pathological retinal neovascularization (RNV) is one of the leading causes of blindness worldwide; however, its underlying mechanism remains unclear. Here, we found that the expression of endothelial protein C receptor (Epcr) was increased during RNV, and its ligand was elevated in the serum or vitreous body of patients with proliferative diabetic retinopathy. Deleting endothelial Epcr or using an EPCR-neutralizing antibody ameliorated pathological retinal angiogenesis. EPCR promoted endothelial heme catabolism and carbon monoxide release through heme oxygenase 1 (HO-1). Inhibition of heme catabolism by deleting endothelial Ho-1 or using an HO-1 inhibitor suppressed pathological angiogenesis in retinopathy. Conversely, supplementation with carbon monoxide rescued the angiogenic defects after endothelial Epcr or Ho-1 deletion. Our results identified EPCR-dependent endothelial heme catabolism as an important contributor to pathological angiogenesis, which may serve as a potential target for treating vasoproliferative retinopathy. |
| format | Article |
| id | doaj-art-eab5933fe7aa420e9bb7a41f177cea98 |
| institution | OA Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-eab5933fe7aa420e9bb7a41f177cea982025-08-20T02:13:06ZengNature PortfolioNature Communications2041-17232025-02-0116111410.1038/s41467-025-56810-0Endothelial protein C receptor promotes retinal neovascularization through heme catabolismHongyuan Song0Qing Li1Xiao Gui2Ziyu Fang3Wen Zhou4Mengzhu Wang5Yuxin Jiang6Ajun Geng7Xi Shen8Yongxuan Liu9Haorui Zhang10Zheng Nie11Lin Zhang12Huimin Zhu13Feng Zhang14Xuri Li15Fanyan Luo16Hongjian Zhang17Wei Shen18Xiaodong Sun19Department of Ophthalmology, Shanghai Changhai HospitalDepartment of Ophthalmology, Shanghai Changhai HospitalDepartment of Ophthalmology, Shanghai Changhai HospitalDepartment of Urology, Shanghai Changhai HospitalDepartment of Ophthalmology, Shanghai Changhai HospitalDepartment of Ophthalmology, Shanghai Changhai HospitalDepartment of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of MedicineKey Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced StudyDepartment of Ophthalmology, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Ophthalmology, Shanghai Changhai HospitalDepartment of Ophthalmology, Shanghai Changhai HospitalDepartment of Ophthalmology, Shanghai Changhai HospitalDepartment of Ophthalmology, Shanghai Changhai HospitalDepartment of Ophthalmology, Shanghai Changhai HospitalState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual ScienceState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual ScienceDepartment of Cardiac Surgery, Xiangya Hospital, Central South UniversityOriental Pan-Vascular Devices Innovation College, University of Shanghai for Science and TechnologyDepartment of Ophthalmology, Shanghai Changhai HospitalDepartment of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of MedicineAbstract Pathological retinal neovascularization (RNV) is one of the leading causes of blindness worldwide; however, its underlying mechanism remains unclear. Here, we found that the expression of endothelial protein C receptor (Epcr) was increased during RNV, and its ligand was elevated in the serum or vitreous body of patients with proliferative diabetic retinopathy. Deleting endothelial Epcr or using an EPCR-neutralizing antibody ameliorated pathological retinal angiogenesis. EPCR promoted endothelial heme catabolism and carbon monoxide release through heme oxygenase 1 (HO-1). Inhibition of heme catabolism by deleting endothelial Ho-1 or using an HO-1 inhibitor suppressed pathological angiogenesis in retinopathy. Conversely, supplementation with carbon monoxide rescued the angiogenic defects after endothelial Epcr or Ho-1 deletion. Our results identified EPCR-dependent endothelial heme catabolism as an important contributor to pathological angiogenesis, which may serve as a potential target for treating vasoproliferative retinopathy.https://doi.org/10.1038/s41467-025-56810-0 |
| spellingShingle | Hongyuan Song Qing Li Xiao Gui Ziyu Fang Wen Zhou Mengzhu Wang Yuxin Jiang Ajun Geng Xi Shen Yongxuan Liu Haorui Zhang Zheng Nie Lin Zhang Huimin Zhu Feng Zhang Xuri Li Fanyan Luo Hongjian Zhang Wei Shen Xiaodong Sun Endothelial protein C receptor promotes retinal neovascularization through heme catabolism Nature Communications |
| title | Endothelial protein C receptor promotes retinal neovascularization through heme catabolism |
| title_full | Endothelial protein C receptor promotes retinal neovascularization through heme catabolism |
| title_fullStr | Endothelial protein C receptor promotes retinal neovascularization through heme catabolism |
| title_full_unstemmed | Endothelial protein C receptor promotes retinal neovascularization through heme catabolism |
| title_short | Endothelial protein C receptor promotes retinal neovascularization through heme catabolism |
| title_sort | endothelial protein c receptor promotes retinal neovascularization through heme catabolism |
| url | https://doi.org/10.1038/s41467-025-56810-0 |
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