3. Mechanisms Of Angiogensis II Flashcards
Outline the tip stalk formation to new blood vessel
- selection of sprouting ECs: ECM degradation, Hif activate growth factors, tip grow towards GFs, lateral inhibition of neighboring cells
- sprout outgrowth and guidance: EC proliferation, migration towards GF gradient, invasion of ECM
- sprout fusion and lumen formation: stalk cell proliferation, vacuole formation and fusion, tip cell adhesion/repulsion
- perfusion and maturation: stabilization of EC-EC adhesion, stabilization of pericyte coverage
Which protein controls bidirectional lateral inhibition in angiogenesis?
Jag1
How does the metabolic state of ECs regulate angiogenesis?
Sense low O2 before HIF is stabilized. Metabolism is changed, control vascular response
How do different VEGF isoforms have different effects?
- differing ability to interact with ECM
- alters diffusibility through ECM
- impacts ability to activate receptors
- impacts receptor clustering
- impacts angiogenesis
How come the interaction of VEGF189 is different?
Has 189 amino acids, veery long chain. Less ability to diffuse
Tip cell selection alters what factors and how:
Downregulates: VEGFR2, DLL4 (inhibition), UNC5B, PDGFB
Upregulates: VEGFR1
How does the endothelial cell metabolism react to hypoxia?
- EC sensitive to hypoxia. Activate Hifa
- upregulation of DLL4
- Silence notch in neighboring cell type
- decrease glycolysis activity
- changes metabolism state by lateral inhibition
- migration towards tumour changes based on metabolic activity
What does glycolysis mean for ATP production and how is this beneficial to the EC?
- Not as much ATP produced
- Respiration via different mechanisms dont require as muc O2/glucose
What sages is metabolic activity highest during angiogenesis?
Sprout elongation, anastomosis, and vessel remodeling
What does VE cadherin do during anastomosis
