Lysyl oxidase interactions with transforming growth factor-β during angiogenesis are mediated by endothelin 1.
Hagar GrunwaldKristina L HunkerIsabelle BirtRohtem AviramShelly Zaffryar-EilotSanthi K GaneshPeleg HassonPublished in: FASEB journal : official publication of the Federation of American Societies for Experimental Biology (2021)
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.
Keyphrases
- transforming growth factor
- vascular endothelial growth factor
- epithelial mesenchymal transition
- vascular smooth muscle cells
- endothelial cells
- signaling pathway
- angiotensin ii
- single cell
- high throughput
- aortic valve
- left ventricular
- pulmonary artery
- heart failure
- cell proliferation
- pulmonary arterial hypertension
- endoplasmic reticulum stress