20 .Angiogenesis Flashcards
Give examples of how different blood vessels arranged in the body?
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
What is the stem cell that is a precursor to both angiogenesis or cells in the blood
Heamangiobalst
Explain the process of angiogenesis (basic overview)
Endothelial progenitor cells
Vasculogenesis
Angio/arteriogenesis
Mature vasculature
Explain the process of maturation of cells in the blood?
Haematopoietic stem cells
T cells, dendrritic cells, neutrophilsm mast cells
How do you define angiogenesis?
Growth of new blood vessels from existing vasculature
Give some physiological examples where angiogenesis is required?
Change to cardiac muscle
Changes to skeletal muscle
Pregnancy
ageing
living at altitude
weight loss/gain
Wound healing
How are blood vessels maintained/grown during angiogenesis?
Recruit vascular smooth muscle cells which release extracellular membrane
Tightening of vessels due to smooth muscle cells
How are blood vessels regressed during angiogenesis?
Infiltration of macrophages
leads to vessel regression
This can due to non-requirement, leakage or damage
Describe the moelcular mechanisms of angiogenesis?
- Release of angiogenic growth factors
- Growth factors activate endothelial cells
- Proteolysis of endothelial matrix
- migration and proliferation of endothelial cells
- sprouting vessles and lumen formatiion
- Vessel maintenence/growth/stabilization
What growth factors stimualtes the majority of angiogenesis
Vascular endothlial factor growth factor (VEGF)
What mechanisms trigger the release of VEGF
Hypoxia triggers release of transcrpition factor:
hypoxia induced factor 1a (HIF 1a)
Describe the actions of HIF 1-a during normoxia?
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
After VEGF is produced, what occurs next?
Binds to VEGF receptor 2. Main receptor involved in angiogenesis.
Thi sis a tyrosine kinase receptor
What is meant by a tyrosine kinase receptor?
Autophosphorylates upon bindign to VEGF leading to activation of signalling cascades.
What is found in the extracellular matrix?
Collagen and elastin (for stretching)
How does stage 3, degredation of extracellular matrix occur?
Enzymes called matrix metalloprotineases dissolve holes in the basement membranes allowing a hole for endothelial cells to migrate through.
What is the job of adhesion molecule integrins?
Serve as grappling hooks to pull the sprouting blood vessel forward
What is vasculogenesis?
What is vessel co-option?
What is vascual mimicry?
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
How does vasculogenesis occur?
Occurs from endothelial progenitor cells
