20 .Angiogenesis

Question 1

Give examples of how different blood vessels arranged in the body?

Answer 1

Blood vessels running parralell to nerves- form long cables parallel to a path of neurons

Muscle- corkscrew shaped so that on compression (contraction) the flow wont be obstructed

Lungs- Blood vessesl wrap around alveolae to maximise gas exchange

Question 2

What is the stem cell that is a precursor to both angiogenesis or cells in the blood

Answer 2

Heamangiobalst

Question 3

Explain the process of angiogenesis (basic overview)

Answer 3

Endothelial progenitor cells

Vasculogenesis

Angio/arteriogenesis

Mature vasculature

Question 4

Explain the process of maturation of cells in the blood?

Answer 4

Haematopoietic stem cells

T cells, dendrritic cells, neutrophilsm mast cells

Question 5

How do you define angiogenesis?

Answer 5

Growth of new blood vessels from existing vasculature

Question 6

Give some physiological examples where angiogenesis is required?

Answer 6

Change to cardiac muscle

Changes to skeletal muscle

Pregnancy

ageing

living at altitude

weight loss/gain

Wound healing

Question 7

How are blood vessels maintained/grown during angiogenesis?

Answer 7

Recruit vascular smooth muscle cells which release extracellular membrane

Tightening of vessels due to smooth muscle cells

Question 8

How are blood vessels regressed during angiogenesis?

Answer 8

Infiltration of macrophages

leads to vessel regression

This can due to non-requirement, leakage or damage

Question 9

Describe the moelcular mechanisms of angiogenesis?

Answer 9

1. Release of angiogenic growth factors
2. Growth factors activate endothelial cells
3. Proteolysis of endothelial matrix
4. migration and proliferation of endothelial cells
5. sprouting vessles and lumen formatiion
6. Vessel maintenence/growth/stabilization

Question 10

What growth factors stimualtes the majority of angiogenesis

Answer 10

Vascular endothlial factor growth factor (VEGF)

Question 11

What mechanisms trigger the release of VEGF

Answer 11

Hypoxia triggers release of transcrpition factor:

hypoxia induced factor 1a (HIF 1a)

Question 12

Describe the actions of HIF 1-a during normoxia?

Answer 12

Rapdily degraded in an oxygen dependent degredatoin domain

This is due to Hippel Lindau protein

Conversely this won’t occur during hypoxia as oxygen can’t drive degredation

Question 13

After VEGF is produced, what occurs next?

Answer 13

Binds to VEGF receptor 2. Main receptor involved in angiogenesis.

Thi sis a tyrosine kinase receptor

Question 14

What is meant by a tyrosine kinase receptor?

Answer 14

Autophosphorylates upon bindign to VEGF leading to activation of signalling cascades.

Question 15

What is found in the extracellular matrix?

Answer 15

Collagen and elastin (for stretching)

Question 16

How does stage 3, degredation of extracellular matrix occur?

Answer 16

Enzymes called matrix metalloprotineases dissolve holes in the basement membranes allowing a hole for endothelial cells to migrate through.

Question 17

What is the job of adhesion molecule integrins?

Answer 17

Serve as grappling hooks to pull the sprouting blood vessel forward

Question 18

What is vasculogenesis?

What is vessel co-option?

What is vascual mimicry?

Answer 18

Vasculogenesis- Bone marrow derived endothelial cells

Vessel co-option- tumour cells pre-opt existing blood vessels instead of making here own

Vascular mimicry- tumours mimic endothelial cells to get nutrients

Question 19

How does vasculogenesis occur?

Answer 19

Occurs from endothelial progenitor cells