Angiogenesis Flashcards
What are the three ways of making blood vessels?
Vasculogenesis – formation of new blood vessels from bone marrow progenitor cells
Angiogensis – formation of new blood vessels by sprouting from pre-existing vessels
Arteriogenesis – collateral growth of blood vessels that is dependent on shear stress and external factors like macrophages
What is the main signal for angiogenesis?
Hypoxia
What is the most important pro-angiogenic factor?
VEGF (Vascular Endothelial Growth Factor)
Explain the mechanism by which hypoxia triggers angiogenesis.
HIF (hypoxia-inducible factor) is a transcription factor that is responsible for the expression of genes involved in angiogenesis
In normoxic conditions, HIF is bound to von Hippel Lindau protein- pVHL (tumour suppressor), which inhibits HIF from promoting angiogenesis
In hypoxic conditions, HIF is not bound to von Hippel Lindau so it can regulate transcription and express genes involved in angiogenesis
How many members are there in the VEGF family? List them.
5
VEGF-A, B, C, D
PIGF (placental growth factor)
How many tyrosine kinase receptors are there for VEGF? List them.
3
VEGFR 1, 2 and 3
How many coreceptors are there for VEGF? List them.
2 Neuropilin 1 (Nrp 1) and 2
Which receptor is the major mediator in VEGF-dependent angiogenesis?
VEGFR2
What pathway is crucial for the selection of tip cells?
Notch signalling
What happens when the notch ligand binds to the notch receptor?
The intracellular NICD domain is cleaved
This then translocates to the nucleus and binds to the transcription factor RBP-J and regulates transcription
What is another name for the notch ligand?
Delta-like ligand (Dll4)
What effect does VEGF have on notch signalling?
VEGF activation increases expression of Dll4
Dll4 drives Notch signalling, which inhibits expression of VEGFR2 in the adjacent cell
Dll4-expressing tip cells acquire a motile, invasive and sprouting phenotype
Adjacent cells (Stalk cells) form the base of the emerging sprout, proliferate to support sprout elongation.
Which cell type is involved in vessel anastomosis and helping stabilise newly formed vessels by promoting tip cell fusion?
Macrophages
Which other cell type is recruited to help with the stabilisation of the newly formed vessel?
Pericytes
Which cell adhesion molecules are essential for vessel stabilisation and quiescence?
Name some of its functions
VE-Cadherin
- expressed at junctions
- maintains adhesion between endothelial cells
- controls contact inhibition of cell growth
- promotes survival of EC