Vasculogenesis and Angiogenesis

Question 1

Vasculogenisis definition

Answer 1

Formation of blood vessels from endothelial progenitor cells. Only in embryonic development

Question 2

Angiogenesis definition

Answer 2

Formation of blood vessels through sprouting of pre-existing vessels. In embryonic development and in adults.

Question 3

Intraembryonicall vasculogenesis

Answer 3

In embryo: angioblast differentiate to endothelial cells in the mesoderm

Question 4

Extraembryonicall vasculogenesis

Answer 4

In the yolk sac: mesenchymal cells → hemangioblasts → angioblasts/HSC → form blood islands which merge to capillaries

Question 5

Steps of Vascular development

Answer 5

1. Angioblasts form in the mesoderm
2. Angioblasts assemble into cords
3. Cord angioblasts form tulles and differentiate to endothelial cells
4. Remodelling and maturation: recruitment of pericytes and smooth muscle cells

Question 6

Steps of Vasculogenesis

Answer 6

1. VEGF binds to VEGF-R2 (FLK 1) receptor → differentiation of endothelial cells (to angioblasts and HSC)
2. VEGF binds to VEGF-R1 (FLt 1) receptor → formation of capillaries and larger blood vessels
3. Angiopoetin 1 bind to Tie 2 → recruitment of pericytes and smooth muscle cells → stabilise new blood vessel

Question 7

Hypoxia induced up regulation of VEGF

Answer 7

Hypoxia blocks PHD (prolyl hydroxylase) to add OH to HIF-1alpha (Hypoxia inducible transcription factor) → HIF-1a binds to DNA and activates VEGF expression

Question 8

Regulators of VEGF

Answer 8

1. Cytokines (TNF-a, IL-6)
2. Growth factors
3. Tumor suppresor genes
4. Hypoxia
5. NO

Question 9

Angiopoetin 1 and 2 functions

Answer 9

1: binds to Tie 2 receptor → recruits perivascular cells → stabilises vessels
2: inhibits Tie 2 signalling (indicted by active remodelling and sprouting of vessels

Question 10

2 types of angiogenesis

Answer 10

1. Sprouting: invasion of new capillaries from preexisting vessels (Degradation → migration → proliferation → tube formation)
2. Intravscular / Intussusception: Incrase in vessel numbers by splitting pre-exsisting vessels

Question 11

Steps of angiogenesis

Answer 11

1. Angiopoetic stimulus (Hypoxia, Injury, Inflammation, Stress)
2. Degradation of basal membrane (proteolytic enzymes from endothelial cells and pericytes)
3. Capillary sprout formation (Endothelial cells form protrusions towards the angiogenic stimulus and invade the ECM)
4. Proliferation of endothelial cells
5. Formation of a lumen (branching, open ends build a loop)
6. Stop endothelial cell migration and proliferation
7. Stabilisation of new blood vessels (recruitment)

Question 12

Pathological angiogenesis causes and effects

Answer 12

Caused by imbalances in stimulating and inhibitory factors.
Effects:
1. Tumor growth
2. Rheumatoid arthitis
3. Atherosclerosis
4. Diabetic retinopathy

Question 13

Lymphangiogenesis

Answer 13

• Starts day 9-10 of embryonic development.
• LEC (Lymphatic endothelial cells) originate from venous endothelial cells in the cardinal vein
• Separation of lymphatic and blood circulation: Platelet activation by binding of PDPN to platelet receptor CLEC-2 required for separation