Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Level 7, 32 Gisborne Street, East Melbourne, VIC, 3002, Australia.
Ophthalmology, Department of Surgery, University of Melbourne, East Melbourne, VIC, Australia.
Angiogenesis. 2024 Nov;27(4):641-661. doi: 10.1007/s10456-024-09942-8. Epub 2024 Aug 29.
Fine-tuning angiogenesis, the development of new blood vessels, is essential for maintaining a healthy circulatory and lymphatic system. The small glycoprotein vascular endothelial growth factors (VEGF) are the key mediators in this process, binding to their corresponding membrane-bound VEGF receptors (VEGFRs) to activate angiogenesis signaling pathways. These pathways are crucial throughout human life as they are involved in lymphatic and vascular endothelial cell permeability, migration, proliferation, and survival. Neovascularization, the formation of abnormal blood vessels, occurs when there is a dysregulation of angiogenesis and can result in debilitating disease. Hence, VEGFRs have been widely studied to understand their role in disease-causing angiogenesis. VEGFR1, also known as Fms-like tyrosine kinase-1 (FLT-1), is also found in a soluble form, soluble FLT-1 or sFLT-1, which is known to act as a VEGF neutralizer. It is incorporated into anti-VEGF therapy, designed to treat diseases caused by neovascularization. Here we review the journey of sFLT-1 discovery and delve into the alternative splicing mechanism that creates the soluble receptor, its prevalence in disease states, and its use in current and future potential therapies.
微调血管生成，即新血管的发育，对于维持健康的循环和淋巴系统至关重要。小糖蛋白血管内皮生长因子 (VEGF) 是这个过程中的关键介质，与它们相应的膜结合 VEGF 受体 (VEGFR) 结合，激活血管生成信号通路。这些通路在人类生命中至关重要，因为它们涉及到淋巴管和血管内皮细胞的通透性、迁移、增殖和存活。新血管形成，即异常血管的形成，发生在血管生成失调时，可能导致衰弱性疾病。因此，广泛研究了 VEGFR 以了解它们在导致疾病的血管生成中的作用。VEGFR1，也称为 Fms 样酪氨酸激酶-1 (FLT-1)，也以可溶性形式存在，即可溶性 FLT-1 或 sFLT-1，已知其作为 VEGF 中和剂发挥作用。它被纳入抗 VEGF 治疗中，旨在治疗由新血管形成引起的疾病。在这里，我们回顾了 sFLT-1 的发现过程，并深入探讨了产生可溶性受体的选择性剪接机制、它在疾病状态下的普遍性，以及它在当前和未来潜在治疗中的应用。
