5. Angiogenesis Flashcards
Recall the 3 mechanisms of vessel formation
- Sprouting
- Arteriogenesis
- Vasculogenesis
What is arteriogenesis?
Collateral growth dependent on shear stress and external factors like macrophages
What is vasculogenesis?
Bone marrow progenitor cell differentiation during development
Where does sprouting occur?
Small vessels
Upon what sort of cells do pro-angiogenic stimuli act?
Endothelial
Summarise the mechanism of sprouting following stimulation
Endothelial cells undergo conformational change - produce filopodia
Migrate towards GFs
Cells behind tip cell proliferate to push it forward
Two tip cells meet –> fusion
How is the tip cell different from surrounding cells in sprouting?
Modified cytoskelton
What is the main trigger for sprouting?
Hypoxia
Describe the mechanism by which hypoxia triggers sprouting
Hypoxia-induced TF (HITF) is bound to a TSG called pVHL in normoxia, released in hypoxia to drive expression of VEGF gene (vasc. endothelial GF)
Name the 5 members of the VEGF family
VEGF-A/B/C/D, PlGF (placental GF)
By what is VEGF detected?
Tyrosine kinase receptors (VEGFR-1,2 and 3)
What is neuropillin?
Co-receptor for VEGF
Recall the 2 coreceptors for VEGF
Neuropillin-1 + 2
How do tip cells stimulate the cells behind them to divide?
- Tip cells express notch ligand, which binds to notch receptors on the cells behind
- Intracellular domain of receptor cleaved = activated
- Cleaved domain translocated to nucleus and binds to a TF called RBP-J
What is the main driver of the cardinal notch pathway?
DII4
