Lecture 20 - Angiogenesis Flashcards
Diagram of Growth Factors & Receptors essential in 1) Vasculogenesis 2) Angiogenesis & 3) Lymphangiogenesis
On summary sheet
What are VEGF critical for? Can you survive without them?
Growth & proliferation of angioblasts (endothelial progenitors). Without them the embryo does not survive. (no vasculogenesis or lymphangiogenesis)
What is angiogenesis?
The formation of new BVs from pre-existing ones.
What is angiopoietin? Is it critical?
The blood vessel making protein. Yes, without it you die however later than you would if you didn’t have VEGF.
Why does Angiogenic Sprouting occur? How does it occur?
Once you have formed a closed system you need to start telling some of the BVs to grow out in a different direction. Uses attractant and repellant molecules (GFs) to do this (e.g. VEGF)
Does Angiogenic Sprouting occur in adults? When are the 3 times?
- Wound healing
- Formation of the placenta
- Cancer development
How do you get the angioblasts to form 2 very different products - e.g. arteries and veins.
Have a homogeneous population (angioblasts sitting close to each other). Switch on two different surface molecules & immediately get two very different products (arteries or veins).
How to the arteries and veins get their different supporting structures? What is one important supporting structure arteries must have? What growth factor does the artery use to get it?
Formation of the different phenotypes (e.g. arteries & veins) then brings with it formation of the different supporting structures.
Arteries develop a lot of vascular smooth muscle cells (vSMC). Veins don’t have this as they are not under the same amount of pressure.
Arteries use the growth factor platelet-derived growth factor-beta (PDGFB) to recruit the vSMC. Without this GF the BVs of the embryo leaks because they are v weak - haemorrhaging & aneurysms
What molecule regulates BBB endothelial development? Is it only found on the brain? Is it highly or lowly expressed?
GPR124 - a glucose transporter. V important! Die without it. Only expressed in the brain & v highly expressed. It is expressed during BBB development but also during cancer.
How does the lymphatic fluid move around the body?
Doesn’t rely on heart to pump it around. Has valves & body movement pushes it around.
Which transcription factor regulates the generation of the lymphatic vessels in the developing embryo? What happens if an embryo doesn’t have this?
Prox1 - without it fluid builds up & it dies
What are the two origins in which the vSMCs/pericytes can potentially be derived from?
- Mesoderm
2. Neural crest
Are large tumours highly or lowly vascularised?
Highly. Avascular tumours can’t expand.
What is the “angiogenic switch”
Separates the mutated oncogenes from forming either 1. a harmless tumour or 2. a lethal tumour. What separates the 2 is lethal tumours undergo angiogenesis.
We can stop tumours growing by targeting the GFs they use to undergo angiogenesis & form new BVs. Why doesn’t this treatment affect any of the other BVs in the body?
The other BVs in the body are no longer undergoing change and therefore are not affected.
