Ang-1 和 VEGF：血管生成的中央调节因子
Molecular and Cellular Biochemistry ( IF 3.5 ) Pub Date : 2024-04-23 , DOI: 10.1007/s11010-024-05010-3
Yuanqin Zhao 1 , Bo Yu 1 , Yanxia Wang 1 , Shiming Tan 1 , Qian Xu 1 , Zhaoyue Wang 1 , Kun Zhou 1 , Huiting Liu 1 , Zhong Ren 1 , Zhisheng Jiang 1

Affiliation  

Key Lab for Arteriosclerology of Hunan Province, International Joint Laboratory for Arteriosclerotic Disease Research of Hunan Province, Institute of Cardiovascular Disease, University of South China, Hengyang, 421001, China.

血管生成素-1 （Ang-1） 和血管内皮生长因子 （VEGF） 是血管生成的中心调节因子，欧博allbet在各种心血管疾病中经常失活。VEGF 与 ETS 转录因子家族形成复合物，并通过下调多个基因来发挥作用。在 VEGF-ETS 复合物的靶基因中，有大量编码关键血管生成调节因子。VEGF-ETS 复合物的磷酸化释放了这些血管生成调节因子的转录抑制，从而促进了它们的表达。Ang-1 与 TEK 相互作用，欧博百家乐这种磷酸化释放可受 Ang-1-TEK 信号通路的调节。Ang-1-TEK 通路参与 VEGF 基因的转录激活。总之，这些元件构成了 Ang-1-TEK-VEGF 信号通路。此外，Ang-1 在缺氧和炎症条件下被激活，导致 TEK 表达上调。TEK 水平升高导致 VEGF-ETS 复合物的形成，进而下调许多血管生成基因的表达。因此，Ang-1 依赖性转录抑制是间接的。许多靶基因的表达降低会导致异常的血管生成。Ang-1-TEK-VEGF 调控的靶基因与受 Ang-1-TEK-TSP-1 信号通路控制的靶基因之间存在显著重叠。从机制上讲，这可以通过在靶基因启动子上的 ETS 位点用 TSP-1 转录抑制复合物替换 VEGF-ETS 复合物来解释。此外，VEGF 具有与 ETS 和 DNA 结合无关的非经典功能。其在 TSP-1 形成中的支持作用可通过 VEGF-CRL5-VHL-HIF-1α-VH032-TGF-β-TSP-1 轴发挥。 本文评估了 Ang-1-TEK-VEGF 信号通路的调控机制，并探讨了其与 Ang-1-TEK-TSP-1 信号通路的显著重叠。

Ang-1 and VEGF: central regulators of angiogenesis

Angiopoietin-1 (Ang-1) and Vascular Endothelial Growth Factor (VEGF) are central regulators of angiogenesis and are often inactivated in various cardiovascular diseases. VEGF forms complexes with ETS transcription factor family and exerts its action by downregulating multiple genes. Among the target genes of the VEGF-ETS complex, there are a significant number encoding key angiogenic regulators. Phosphorylation of the VEGF-ETS complex releases transcriptional repression on these angiogenic regulators, thereby promoting their expression. Ang-1 interacts with TEK, and this phosphorylation release can be modulated by the Ang-1-TEK signaling pathway. The Ang-1-TEK pathway participates in the transcriptional activation of VEGF genes. In summary, these elements constitute the Ang-1-TEK-VEGF signaling pathway. Additionally, Ang-1 is activated under hypoxic and inflammatory conditions, leading to an upregulation in the expression of TEK. Elevated TEK levels result in the formation of the VEGF-ETS complex, which, in turn, downregulates the expression of numerous angiogenic genes. Hence, the Ang-1-dependent transcriptional repression is indirect. Reduced expression of many target genes can lead to aberrant angiogenesis. A significant overlap exists between the target genes regulated by Ang-1-TEK-VEGF and those under the control of the Ang-1-TEK-TSP-1 signaling pathway. Mechanistically, this can be explained by the replacement of the VEGF-ETS complex with the TSP-1 transcriptional repression complex at the ETS sites on target gene promoters. Furthermore, VEGF possesses non-classical functions unrelated to ETS and DNA binding. Its supportive role in TSP-1 formation may be exerted through the VEGF-CRL5-VHL-HIF-1α-VH032-TGF-β-TSP-1 axis. This review assesses the regulatory mechanisms of the Ang-1-TEK-VEGF signaling pathway and explores its significant overlap with the Ang-1-TEK-TSP-1 signaling pathway.