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<p>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 (<i>Epcr</i>) was increased during RNV, and its ligand was elevated in the serum or vitreous body of patients with proliferative diabetic retinopathy. Deleting endothelial <i>Epcr</i> 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 <i>Ho-1</i> or using an HO-1 inhibitor suppressed pathological angiogenesis in retinopathy. Conversely, supplementation with carbon monoxide rescued the angiogenic defects after endothelial <i>Epcr</i> or <i>Ho-1</i> 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.</p>

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Endothelial protein C receptor promotes retinal neovascularization through heme catabolism

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年2月13日

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  • 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

摘要

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.