L16-17: Vasculature Development Flashcards

1
Q

Are signalling pathways in veins and arteries different?

A

No.

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2
Q

What does ephrin B2 signalling do?

A
  • promote directional cell migration and invasion

- suppress cell apoptosis

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3
Q

What is angiogenesis and vasculogenesis?

A

Vasculogenesis is formation of new blood vessels

Angiogenesis is branching from existing vessels to create new ones

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4
Q

Cell transitions in becoming blood vessels

A

mesoderm > hemangioblasts > angioblasts > endothelial cells

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5
Q

Where is extraemryonic vasculogenesis taking place?

A

in the yolk sac

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6
Q

Where is intraembryogenic vasculogenesis taking place?

A

dorsal aorta and vessels between organs

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7
Q

What are the steps in vasculogenesis?

A
  1. condensation
  2. Differentiation
  3. epithelialization
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8
Q

What inhibits the proliferation of endothelial cells?

A

contact with the capillary basement membrane

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9
Q

What are some markers of quiescent endothelial cells?

A

PECAM, L-selectin

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10
Q

What are some markers of angiogenic endothelial cells?

A

TFG-β receptor

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11
Q

What are the three types of endothelial cells? Where are they found

A

continuous. muscle, brain, heart

fenestrated, discontinuous. endo/exocrine organs. for easier transport

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12
Q

what the big difference between discontinous and continous/fenestrated endo cells

A

No basal membrane on discontinuous

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13
Q

What are some support cells that wrap around the endothelial cells?

A

pericytes and other mural cells

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14
Q

What connects mural cells to endo cells?

A

angiopoetins on mural cells and Tie2 receptors on endo cells

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15
Q

What type of cell give rise to endo and mural cells?

A

vascular progenitor

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16
Q

Which VEGFR can exist in free soluble but inactive form?

A

VEGFR1

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17
Q

Which receptors can bind VEGFA?

A

VEGFR 1 and 2

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18
Q

Which VEGFR is not necessary in angiogenesis?

A

VEGFR 3

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19
Q

What would happen without mural cells?

A

severe edema. makes sense because there would vasodialation without control?

20
Q

What is interesting about VEGFR1 role in vasculogenesis?

A

Even without the kinase domain, it had no negative effect on vasculogenesis. But total removal results in lower vasculogenesis.

21
Q

What is the primary role of VEGFR1?

A

Recruit macrophages to release

22
Q

What is essential for vasculogensis and what is not?

A

VEGFR2 and VEGFA is.

VEGFR1 is not

23
Q

What are three functions of VEGFR2?

A

proliferation, survival and motility

24
Q

Describe how boyden chamber assay works

A

Plate cells. Put chemoattractants and see the migration of the cells above or below the plate

25
Q

VEGF in angiogenesis. What does it do?

A
  • FAK pathway > stress fibre and focal adhesion > cell migration towards VEGF source
  • cell proliferation
  • tube formation
26
Q

What part leads to the formation of vascular tube?

A

intracellular vacuoles

27
Q

Difference between VEGF and bFGF?

A

VEGF is specific for endo cells. bFGF is not.

28
Q

What is non sprouting angiogenesis and how does it happen?

A

fibroblasts wrap around the vessels to form pillars and split in half.

29
Q

What kind of remodelling can be done during angiogenesis? How?

A

splitting and removal of vessels. Through pillar formation

30
Q

What process ensures that only one cell becomes tip cell?

A

lateral inhibition

31
Q

Explain lateral inhibition

A

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

32
Q

How are veins and arteries merged together?

A

EphB4 on veins and Epherin B2 on arteries. Reverse signalling.

33
Q

Describe reverse signalling on eph pathway

A

On the ligand side, the signalling downstream happens.

34
Q

What happens in forward and reverse signalling in eph pathway for angiogenesis.

A

forward. Repulsion

Backward. cell migration

35
Q

Which direction of eph signalling defines the boundaries between arteries and veins?

A

forward

36
Q

How do tumors abuse eph signalling?

A

overproduce ephB4 to form more arteries towards it.

37
Q

How far is every cell from a capillary?

A

50-100μm

38
Q

Does angiogenesis happen during injury?

A

ya. duh

39
Q

What happens in hypoxia? Details

A

hypoxia > HIF1α is not degraded > binds with β > becomes a transcriptional factor > VEGF

40
Q

How is angiogenesis basal membrane breakdown possible?

A

MMP

41
Q

What are two types of MMP and what they break down

A

MMP2(gelatinase A) - collagen I, IV, V, fibrillar collagen

MMP9(gelatinase B) - collagen IV, V

42
Q

Are MMPs pro or anti angiogenic?

A

both

43
Q

How does VEGF increase permiability?

A

VEGF > Fak > bind to cadherine > βcatening released > no adherens junction

44
Q

Explain how MMPs are anti angiogenic

A
  • can increase competition for MMP2

- cleave ligand binding domain of VEGFR1

45
Q

Explain how MMPs are pro angiogenic

A
  • basal membrane disintegration
  • MMP2 bind to integrins
  • release more VEGF
  • cleavage of VE-cadherins
  • release bFGF and activate TGFβ