Angiogenesis Flashcards
What are the 2 ways for endothelial cell development and formation of new vessels?
- Vasculogenesis: de novo, from stem cells (from angioblasts to vascular plexus)
- Angiogenesis (from pre-existing vessels):
- sprouting angiogenesis => with “tip cells” (endothelial cell) reaching outwards followed by “stalk cells” (basement membrane and pericyte)
- intussusception => dividing vessels
What is VEGF-A?
Main ligand for blood vessel formation with VEGF receptor (VEGFR)
Need for dimer formation
What is VEGFR2, how does it circulate in the membrane and how does it activate?
- Main receptor for vasculogenesis and angiogenesis
- VEGFR2 monomers move around in the cell membrane => stabilize when becomes dimer from dimer ligand (VEGF-A)
- VEGFR2 dimers phosphorylate each other => signal transduction
What are the functions of all 3 VEGFR?
- VEGFR1 = vascular permeability
- VEGFR2 = vasculogenesis and angiogenesis
- VEGFR3 = vasculogenesis and lymphangiogenesis
What is PDGF-B, what does it bind to and what is its function?
It is a growth factor protein secreted by tip cells to attract pericytes on the growing vessel via binding on PDGFR-ß on the pericytes
For what can PDGFR-ß be used as a marker and what is the consequence when mutated?
- Marker for pericytes and vascular smooth muscle cells
- Factor-independent pro-angiogenic effect, can lead to embryonic development problems
What are the 3 main function of blood vessels?
- Supply with nutrients, transport of metabolites
- Transport of blood/immune cells
- O2/CO2 exchange
What is the main source of cellular ATP production in blood endothelial cells (BECs) and what are the 3 reasons why?
- When available glucose is unlimited, glycolysis can produce more ATP in a shorter time span than oxidative phosphorylation, thereby allowing BECs to quickly sprout and form new vessels
- By being independent of oxygen, BECs have the advantage to be able to sprout into hypoxic or even anoxic tissues as long as glucose is present
- Glucose can shunt glycolytic intermediates into side branches of glycolysis where they can be used for the synthesis of macromolecules and generation of reducing power for redox homeostasis
What is HIF-⍺ and what is its function?
HIF-⍺ = transcription factor that binds to HRE sequence
In normoxia: HIF-⍺ is inhibited
In hypoxia: HIF-⍺ is free to function (because O2 co-substrate missing for inhibiting enzymes) transcribes HRE => angiogenesis, erythropoiesis, cell proliferation, etc.
What is the angiogenic switch?
Angiogenic switch = when dormant carcinomas “wake up” and start angiogenesis
Can anti-angiogenic therapy be used against cancer?
Theoretically yes but in practice it has limited efficacy and development of resistance
What is the objective with anti-angiogenic therapy?
Normalize tumor vasculature (instead of trying to kill it)
and can also provide radiotherapy window of opportunity
What are the functions of the lymphatic vascular system?
- Fat absorption (intestine)
- Cholesterol transport
- Immunity and immunosurveillance (immune cell and antigen transportation to the lymph node)
Where is the most common metastatic site and why?
- Regional and distant secondary lymph nodes
- Some organs (like skin) are naturally rich in lymphatic vessels => contributing factor to a high incidence of lymphatic metastasis
What is the difference between inflamed and tumor lymph nodes?
Inflammation/Infection : lymph nodes are enlarged, feels warm and gives pain at palpation (firm in texture)
Tumour or metastasis : lymph nodes are enlarged, fixed and firm texture at palpation, no pain, and the lymph nodes have been enlarged over a longer period
