9.2

Question 1

Question:What is the primary function of VEGF-A among the VEGF isoforms?

Answer 1

Answer:VEGF-A stimulates angiogenesis and increases vascular permeability.

Question 2

Question:What role does VEGF-B play in the body?

Answer 2

Answer:VEGF-B is involved in cardiac muscle survival and lipid metabolism.

Question 3

Question:How does VEGF-C contribute to the lymphatic system?

Answer 3

Answer:VEGF-C regulates the formation of lymphatic vessels.

Question 4

Question:What is the function of Placental Growth Factor (PIGF)?

Answer 4

Answer:PIGF supports angiogenesis during pregnancy.

Question 5

Question:Which VEGF receptor is the major mediator of angiogenesis and endothelial cell proliferation?

Answer 5

Answer:VEGFR-2 (KDR/Flk-1) is the major mediator of angiogenesis, vascular permeability, and endothelial cell proliferation.

Question 6

Question:What is the primary ligand for VEGFR-3, and what process does it regulate?

Answer 6

Answer:VEGFR-3 primarily binds VEGF-C and regulates lymphangiogenesis.

Question 7

Question:How does hypoxia regulate VEGF expression?

Answer 7

Answer:Hypoxia reduces prolyl hydroxylase activity, stabilizing HIF-1α, which binds to hypoxia response elements (HREs) in the VEGF gene promoter to increase VEGF transcription.

Question 8

Question:What are the key differences between physiological and pathological angiogenesis?

Answer 8

Answer:Physiological angiogenesis is orderly, balanced, and supports tissue repair, while pathological angiogenesis is chaotic, excessive, and contributes to diseases like cancer and diabetic retinopathy.

Question 9

Question:How do neuropilins (NRPs) enhance VEGF signaling?

Answer 9

Answer:NRPs bind specific VEGF isoforms, stabilize VEGF-VEGFR complexes, and ensure proper ligand-receptor selectivity, amplifying signals for angiogenesis or lymphangiogenesis.

Question 10

Question:What are the clinical implications of targeting VEGF in cancer treatment?

Answer 10

Answer:Inhibiting VEGF signaling can reduce pathological angiogenesis in tumors, slowing growth and metastasis, but risks include vascular leakage and long-term safety concerns.

Question 11

Question:How does VEGF contribute to ischemic diseases like myocardial infarction?

Answer 11

Answer:VEGF promotes compensatory angiogenesis to restore blood flow, but inadequate production or elevated anti-angiogenic mediators can limit recovery.

Question 12

Question:What is the role of Sai Luo Tong (SLT) in vascular dementia?

Answer 12

Answer:SLT improves cerebral blood flow, enhances endothelial cell migration via the PI3K pathway, and promotes angiogenesis in vascular insufficiency models.

Question 13

Question:What are the limitations of pro-angiogenic therapies for ischemic diseases?

Answer 13

Answer:Risks include excessive VEGF production causing vascular leakage, potential pro-tumorigenic effects, and poor central nervous system penetration of some drugs.

Question 14

Question:How does VEGFR-2 activation via phosphorylation at Y1175 affect endothelial cells?

Answer 14

Answer:Phosphorylation at Y1175 activates eNOS, promoting endothelial cell proliferation and migration.

Question 15

Question:What diseases are linked to insufficient angiogenesis?

Answer 15

Answer:Chronic wounds, coronary heart disease, peripheral arterial disease, stroke, and infertility are associated with insufficient angiogenesis.

Question 16

Question:What diseases result from excessive angiogenesis?

Answer 16

Answer:Cancer, diabetic retinopathy, rheumatoid arthritis, and psoriasis are linked to excessive angiogenesis.

Question 17

Question:How do tumor cells exploit VEGF for growth?

Answer 17

Answer:Tumor cells release VEGF under hypoxia to induce pathological angiogenesis, creating leaky vessels that supply nutrients and facilitate metastasis.

Question 18

Question:What strategies are used to manage ischemic diseases by targeting angiogenesis?

Answer 18

Answer:Stem cell therapy and drugs that stabilize HIF-1α or activate VEGFR are used to promote new vessel formation in ischemic tissues.

Question 19

Question:What is the significance of the Phase III clinical trial for Sai Luo Tong (SLT)?

Answer 19

Answer:The trial evaluates SLT’s efficacy in treating vascular dementia and Alzheimer’s with cerebrovascular disease, aiming to improve cerebral blood flow and cognitive function.

Question 20

Question:How does VEGF-B influence VEGFR-2 activity?

Answer 20

Answer:VEGF-B displaces VEGF-A from VEGFR-1, increasing VEGF-A availability to activate VEGFR-2 and enhance angiogenesis.

Question 21

Question:What structural feature is common to all VEGF isoforms?

Answer 21

Answer:All VEGF isoforms are glycoproteins that dimerize in an anti-parallel, side-by-side orientation.

Question 22

What is the structural composition of VEGF? VEGF is composed of glycoproteins (40-45 kDa) that form homodimers in an antiparallel

Answer 22

side-by-side orientation.

Question 23

What are the five isoforms of VEGF and their primary functions? The five isoforms are VEGF-A (stimulates angiogenesis and vascular permeability)

Answer 23

VEGF-B (involved in cardiac muscle survival and lipid metabolism)

Question 24

What are the three main VEGF receptors

Answer 24

their ligands

Question 25

How is VEGFR-1 activated

Answer 25

and what is its downstream effect?  VEGFR-1 is phosphorylated at Y1213

Question 26

What are the key phosphorylation sites and functions of VEGFR-2?  VEGFR-2 phosphorylation at Y951 activates Src kinase for cytoskeleton organization

Answer 26

Y1175 activates eNOS for endothelial proliferation/migration

Question 27

How does VEGFR-3 signaling occur

Answer 27

and what processes does it regulate?  VEGFR-3 is phosphorylated at Y1337

Question 28

What role do neuropilins (NRPs) play in VEGF signaling?  NRPs (NRP-1 and NRP-2) bind specific VEGF isoforms

Answer 28

amplify signals by stabilizing VEGF-VEGFR complexes

Question 29

How does hypoxia regulate VEGF expression via HIF-1α?  Hypoxia inhibits prolyl hydroxylase (PHD)

Answer 29

stabilizing HIF-1α

Question 30

What distinguishes physiological from pathological angiogenesis?  Physiological angiogenesis is orderly

Answer 30

driven by metabolic demands

Question 31

How do tumor cells exploit VEGF for growth and metastasis?  Tumor cells release VEGF under hypoxia to induce pathological angiogenesis

Answer 31

creating disorganized

Question 32

What are four drugs that target VEGF signaling in cancer treatment?  Bevacizumab (anti-VEGF antibody)

Answer 32

aflibercept (VEGF trap)

Question 33

Why is natural compensatory angiogenesis insufficient in ischemic diseases?  Inadequate pro-angiogenic mediators (e.g.

Answer 33

VEGF) and elevated anti-angiogenic factors limit blood vessel formation in conditions like myocardial ischemia

Question 34

What strategies are used to promote angiogenesis in ischemic diseases?  Stem cell therapy enhances HIF-1α signaling and VEGF/eNOS activation

Answer 34

while drugs stabilize HIF-1α or activate VEGFR to stimulate new vessel formation.

Question 35

What are the limitations of pro-angiogenic therapies?  Risks include excessive VEGF causing vascular leakage

Answer 35

potential tumor promotion

Question 36

How does Sai Luo Tong (SLT) improve vascular dementia?  SLT increases cerebral blood flow in the frontal and temporal lobes

Answer 36

enhances endothelial proliferation/migration via PI3K

Question 37

What are the key components of SLT

Answer 37

and what is its current clinical status?  SLT contains Panax ginseng

Question 38

What diseases result from insufficient angiogenesis?  Chronic wounds

Answer 38

coronary heart disease

Question 39

What diseases result from excessive angiogenesis?  Cancer

Answer 39

diabetic retinopathy

Question 40

How does VEGF-B modulate VEGFR-2 activity?  VEGF-B displaces VEGF-A from VEGFR-1

Answer 40

increasing VEGF-A availability to activate VEGFR-2 and enhance angiogenesis.

Question 41

What is the role of endothelial cell behavior in pathological angiogenesis?  In pathological angiogenesis

Answer 41

endothelial cells exhibit chaotic sprouting