Nature communications · 2025
Endothelial protein C receptor promotes retinal neovascularization through heme catabolism.
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Song Hongyuan, Li Qing, Gui Xiao, Fang Ziyu, Zhou Wen, Wang Mengzhu, Jiang Yuxin, Geng Ajun, Shen Xi, Liu Yongxuan, Zhang Haorui, Nie Zheng, Zhang Lin, Zhu Huimin, Zhang Feng, Li Xuri, Luo Fanyan, Zhang Hongjian, Shen Wei, Sun Xiaodong
Аннотация
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.