9.2

Question 1

What does VEGF stand for?

Answer 1

Vascular Endothelial Growth Factor.

Question 2

What is the structure of VEGF proteins?

Answer 2

Glycoproteins (40–45 kDa), forming anti-parallel side-by-side dimers.

Question 3

Name the 5 major isoforms of VEGF and their primary roles.

Answer 3

VEGF-A (angiogenesis), VEGF-B (cardiac muscle & lipid metabolism), VEGF-C/D (lymphangiogenesis), PlGF (placental angiogenesis).

Question 4

What are the three main VEGF receptors?

Answer 4

VEGFR-1 (Flt-1), VEGFR-2 (KDR/Flk-1), VEGFR-3 (Flt-4).

Question 5

What cells express VEGFR-1 and what does it regulate?

Answer 5

Endothelial cells and monocytes; regulates angiogenesis and permeability.

Question 6

What is the key function of VEGFR-2?

Answer 6

Major mediator of angiogenesis, vascular permeability, and endothelial proliferation.

Question 7

What is the main role of VEGFR-3?

Answer 7

Regulates lymphatic vessel formation and maintenance.

Question 8

What are the key phosphorylation sites on VEGFR2 and their roles?

Answer 8

Y951 (Src kinase, migration), Y1175 (eNOS activation, proliferation), Y1214 (p38 MAPK, actin remodelling).

Question 9

What is the function of VEGFR1’s high VEGF-A affinity?

Answer 9

Acts as a decoy receptor; modulates VEGFR2 activity indirectly.

Question 10

How does VEGF-B influence VEGFR2 activity?

Answer 10

It does not trigger downstream signalling but competes with VEGF-A, enhancing VEGFR2 signalling.

Question 11

What is the function of NRPs in VEGF signalling?

Answer 11

Enhance ligand binding, amplify signalling, and regulate ligand-receptor selectivity.

Question 12

Which VEGF isoforms bind to NRP-1?

Answer 12

VEGF-A165, VEGF-B, PlGF.

Question 13

Which isoforms bind NRP-2?

Answer 13

VEGF-C and VEGF-D.

Question 14

What does the NRP-1 + VEGFR-2 complex promote?

Answer 14

Angiogenesis and vascular permeability.

Question 15

What does NRP-2 + VEGFR-3 facilitate?

Answer 15

Lymphangiogenesis.

Question 16

How does hypoxia regulate VEGF expression?

Answer 16

↓O₂ inhibits prolyl hydroxylase → stabilises HIF-1α → binds HRE in VEGF promoter → ↑VEGF transcription.

Question 17

What is HIF-1α?

Answer 17

A transcription factor activated under hypoxia that increases VEGF expression.

Question 18

What triggers physiological angiogenesis?

Answer 18

Controlled hypoxia, developmental signals, metabolic demands.

Question 19

What triggers pathological angiogenesis?

Answer 19

Chronic inflammation, persistent hypoxia, metabolic dysregulation.

Question 20

How is VEGF signalling different in pathological angiogenesis?

Answer 20

Overactive, imbalanced, with dysregulated mediators.

Question 21

Describe endothelial cell behavior in physiological angiogenesis.

Answer 21

Ordered sprouting, regulated proliferation, coordinated pericyte recruitment.

Question 22

Describe endothelial behavior in pathological angiogenesis.

Answer 22

Chaotic sprouting, excessive proliferation, abnormal migration and junctions.

Question 23

Compare vessel structure in physiological vs pathological angiogenesis.

Answer 23

Physiological: organised with normal permeability; Pathological: disorganised, tortuous, leaky vessels.

Question 24

What is the tumour stroma composed of?

Answer 24

New blood vessels, inflammatory cells, connective tissue, and fibrin matrix.

Question 25

How do tumours promote angiogenesis?

Answer 25

Release VEGF → increases vessel permeability and reduces selectivity.

Question 26

How does this affect immune cell infiltration?

Answer 26

Enhanced by leaky neovessels in tumours.

Question 27

Why is VEGF a target in cancer therapy?

Answer 27

Blocking VEGF can limit tumour blood supply and growth.

Question 28

Name two therapeutic strategies to inhibit VEGF.

Answer 28

Anti-VEGF antibodies (e.g., bevacizumab), VEGFR tyrosine kinase inhibitors.

Question 29

Why is natural angiogenesis insufficient in ischemic disease?

Answer 29

Due to low pro-angiogenic and high anti-angiogenic mediator levels.

Question 30

How can stem cell therapy help ischemic tissues?

Answer 30

Promotes angiogenesis via ↑HIF-1α, VEGF, and eNOS activation.

Question 31

How do pro-angiogenic drugs work in ischemia?

Answer 31

Stabilise HIF-1α, enhance VEGFR signalling.

Question 32

What are three key risks of pro-angiogenic therapy?

Answer 32

1) Vascular leakage, 2) Pro-tumorigenic effects, 3) Poor CNS penetration.

Question 33

What is SLT?

Answer 33

A Chinese herbal formula with Panax ginseng, Ginkgo biloba, and Crocus sativus.

Question 34

What effect does SLT have on cerebral blood flow?

Answer 34

Increases CBF in inferior frontal lobe and anterior temporal regions (esp. left).

Question 35

How does SLT promote angiogenesis?

Answer 35

Via PI3K signalling → ↑ endothelial proliferation and migration.

Question 36

What model demonstrated SLT's vascular benefit?

Answer 36

Zebrafish with VEGFR inhibitor-induced vascular insufficiency.

Question 37

What is the clinical status of SLT?

Answer 37

Currently in Phase 3 trials for vascular dementia.