L16-17: Vasculature Development Flashcards
Are signalling pathways in veins and arteries different?
No.
What does ephrin B2 signalling do?
- promote directional cell migration and invasion
- suppress cell apoptosis
What is angiogenesis and vasculogenesis?
Vasculogenesis is formation of new blood vessels
Angiogenesis is branching from existing vessels to create new ones
Cell transitions in becoming blood vessels
mesoderm > hemangioblasts > angioblasts > endothelial cells
Where is extraemryonic vasculogenesis taking place?
in the yolk sac
Where is intraembryogenic vasculogenesis taking place?
dorsal aorta and vessels between organs
What are the steps in vasculogenesis?
- condensation
- Differentiation
- epithelialization
What inhibits the proliferation of endothelial cells?
contact with the capillary basement membrane
What are some markers of quiescent endothelial cells?
PECAM, L-selectin
What are some markers of angiogenic endothelial cells?
TFG-β receptor
What are the three types of endothelial cells? Where are they found
continuous. muscle, brain, heart
fenestrated, discontinuous. endo/exocrine organs. for easier transport
what the big difference between discontinous and continous/fenestrated endo cells
No basal membrane on discontinuous
What are some support cells that wrap around the endothelial cells?
pericytes and other mural cells
What connects mural cells to endo cells?
angiopoetins on mural cells and Tie2 receptors on endo cells
What type of cell give rise to endo and mural cells?
vascular progenitor
Which VEGFR can exist in free soluble but inactive form?
VEGFR1
Which receptors can bind VEGFA?
VEGFR 1 and 2
Which VEGFR is not necessary in angiogenesis?
VEGFR 3
What would happen without mural cells?
severe edema. makes sense because there would vasodialation without control?
What is interesting about VEGFR1 role in vasculogenesis?
Even without the kinase domain, it had no negative effect on vasculogenesis. But total removal results in lower vasculogenesis.
What is the primary role of VEGFR1?
Recruit macrophages to release
What is essential for vasculogensis and what is not?
VEGFR2 and VEGFA is.
VEGFR1 is not
What are three functions of VEGFR2?
proliferation, survival and motility
Describe how boyden chamber assay works
Plate cells. Put chemoattractants and see the migration of the cells above or below the plate
VEGF in angiogenesis. What does it do?
- FAK pathway > stress fibre and focal adhesion > cell migration towards VEGF source
- cell proliferation
- tube formation
What part leads to the formation of vascular tube?
intracellular vacuoles
Difference between VEGF and bFGF?
VEGF is specific for endo cells. bFGF is not.
What is non sprouting angiogenesis and how does it happen?
fibroblasts wrap around the vessels to form pillars and split in half.
What kind of remodelling can be done during angiogenesis? How?
splitting and removal of vessels. Through pillar formation
What process ensures that only one cell becomes tip cell?
lateral inhibition
Explain lateral inhibition
Single cell with many delta binds to multiple cells with notch. This inhibits all cells with notch. So only one cell produces VEGFR2 and migrates
How are veins and arteries merged together?
EphB4 on veins and Epherin B2 on arteries. Reverse signalling.
Describe reverse signalling on eph pathway
On the ligand side, the signalling downstream happens.
What happens in forward and reverse signalling in eph pathway for angiogenesis.
forward. Repulsion
Backward. cell migration
Which direction of eph signalling defines the boundaries between arteries and veins?
forward
How do tumors abuse eph signalling?
overproduce ephB4 to form more arteries towards it.
How far is every cell from a capillary?
50-100μm
Does angiogenesis happen during injury?
ya. duh
What happens in hypoxia? Details
hypoxia > HIF1α is not degraded > binds with β > becomes a transcriptional factor > VEGF
How is angiogenesis basal membrane breakdown possible?
MMP
What are two types of MMP and what they break down
MMP2(gelatinase A) - collagen I, IV, V, fibrillar collagen
MMP9(gelatinase B) - collagen IV, V
Are MMPs pro or anti angiogenic?
both
How does VEGF increase permiability?
VEGF > Fak > bind to cadherine > βcatening released > no adherens junction
Explain how MMPs are anti angiogenic
- can increase competition for MMP2
- cleave ligand binding domain of VEGFR1
Explain how MMPs are pro angiogenic
- basal membrane disintegration
- MMP2 bind to integrins
- release more VEGF
- cleavage of VE-cadherins
- release bFGF and activate TGFβ
