Department of Genetics and Developmental Biology, The Rappaport Faculty of Medicine and Research Institute, Technion - Israel Institute of Technology, Haifa, Israel.
Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.
FASEB J. 2021 Sep;35(9):e21824. doi: 10.1096/fj.202001860RR.
Crosstalk between multiple components underlies the formation of mature vessels. Although the players involved in angiogenesis have been identified, mechanisms underlying the crosstalk between them are still unclear. Using the ex vivo aortic ring assay, we set out to dissect the interactions between two key angiogenic signaling pathways, vascular endothelial growth factor (VEGF) and transforming growth factor β (TGFβ), with members of the lysyl oxidase (LOX) family of matrix modifying enzymes. We find an interplay between VEGF, TGFβ, and the LOXs is essential for the formation of mature vascular smooth muscle cells (vSMC)-coated vessels. RNA sequencing analysis further identified an interaction with the endothelin-1 pathway. Our work implicates endothelin-1 downstream of TGFβ in vascular maturation and demonstrate the complexity of processes involved in generating vSMC-coated vessels.
多种成分之间的串扰是成熟血管形成的基础。虽然已经确定了参与血管生成的参与者，但它们之间串扰的机制仍不清楚。使用离体主动脉环测定法，我们着手剖析两个关键的血管生成信号通路血管内皮生长因子(VEGF)和转化生长因子β(TGFβ)与赖氨酰氧化酶(LOX)家族基质修饰酶成员之间的相互作用。我们发现 VEGF、TGFβ 和 LOX 之间的相互作用对于形成成熟的血管平滑肌细胞(vSMC)包被的血管是必不可少的。RNA 测序分析进一步鉴定了与内皮素-1 途径的相互作用。我们的工作表明 TGFβ 下游的内皮素-1 参与血管成熟，并证明了生成 vSMC 包被血管所涉及的过程的复杂性。
