Endothelial cells and angiogenesis

Question 1

What is angiogenesis?

Answer 1

Process by which new blood vessels are formed

Required many growth factors interacting together to promote the growth of blood vessels

Question 2

When does angiogenesis happen in aults?

Answer 2

Reproduction

Wound healing

Due to low cell turnover

Question 3

What is neovascularization?

Answer 3

Disease-associated angiogenesis and adults

Question 4

What is an important growth factor in angiogenesis?

Answer 4

VEGF

Vascular Endothelial Growth Factor

Question 5

Characteristics of VEGF

Answer 5

Secreted polypeptide

Binds to CS receptors on endothelial cells to regulate cell behaviour

Question 6

Three roles of VEGF

Answer 6

Mitogen

Chemoattractant

Survival factor

Question 7

What does the loss of one copy of the VEGF gene lead to?

Answer 7

Aberrant blood vessel formation and death in embryogenesis

Question 8

What does VEGF do in pathology?

Answer 8

Regulates angiogenesis in many tumours and neovascular diseases

Question 9

Describe the different mechanisms of blood vessel formation

Answer 9

Sprouting angiogenesis

Vasculogenesis

Intussusception

Vessel co-option

Question 10

What is sprouting angiogenesis?

Answer 10

Endothelial cell becomes tip cell

Due to surrounding microenvironment

Question 11

What is vasculogenesis?

Answer 11

Fromation of new blood vessels from endothelial progenitor cells in bone marrow

Question 12

What is intussusception?

Answer 12

Formation of blood vessel within a blood vessel

Branches to form new vessels

Question 13

What is vessel co-option?

Answer 13

Often seen in tumours

Group of cells come together and surround the blood vessel

Forms own blood supply

Question 14

What are the 4 roles of adult angiogenesis?

Answer 14

Physiological roles - embryonic development, wound repair

Pathophysiological role - cancer

Cardiovascular disease - not enough angiogenesis = MI

Diabeted

Question 15

Angiogenesis plays a very important role in cancer

TRUE or FALSE

Answer 15

TRUE

Angiogenic switch is an important factor in the development of a tumour

Question 16

Describe the process of tumourgenesis

Answer 16

Somatic mutation - deletion or change in gene which gives it growth advantage to other cells

Formation of avascular tumour

As tumour grows it secretes angiogenic factors that stimulate angiogenesis of adjacent vessels

Formation of blood vessels into the tumour

Question 17

How do blood vessels provide beneficial effects to the tumour?

Answer 17

Helps the tumour grow by providing it oxygen and nutrients

Provides highway for the tumour cells to extravasculate

Question 18

How does a tumour stimulate angiogenesis?

Answer 18

Secretes angiogenic factors that stimulatre angiogenesis of adjacent vessels

Question 19

What is the angiogenic switch?

Answer 19

Switch in balance from anti- to pro-angiogenic factors

Question 20

What is the balance of angiogenic like in normal conditions?

Answer 20

Production of anti-angiogenic factors help offset the production of pro-angiogenic factors

Question 21

Why does tumourgenesis cause angiogenic switch?

Answer 21

High production of pro-angiogenic factors in surrounding blood vessels

Due to secretion by tumour cells

Leads to imbalance

And switch to pro-angigenic phenotype

Question 22

What are pro-angiogenic factors?

Answer 22

VEGF, FGF, PDGF

Question 23

What are anti-angiogenic factors?

Answer 23

Angiostatin, Endostanin, Thrombospondin

Question 24

What does the vascular network of a normal tissue look like?

Answer 24

Distinct vessel length

Distinct branch points

Question 25

What does the vascular network of a tumour look like?

Answer 25

Chaotic architecture

Leaky

Areas of hypoxia

Thicker vessels

Question 26

What does the tumour vasculature mean for the delivery of therapies?

Answer 26

Abnormalities reduce the delivery of therapies to the tissues

Question 27

What is HIF-1?

Answer 27

Hypoxia inducible factor 1

Master regulator of the hypoxic response

Question 28

Where is HIF 1 found?

Answer 28

In cells

Question 29

What does HIF 1 do?

Answer 29

Regulator of tumour survival, progression and metastasis

HIF 1 is associated with increased patient mortality

Question 30

What dos HIF 1 cause expression of?

Answer 30

VEGF

Question 31

What happens to HIF 1 in oxygenated cells?

Answer 31

HIF - PH enxyme flags the degradation of HIF via proteasome pathways

Question 32

What happens to HIF 1 in low levels of oxygen?

Answer 32

No HIF breakdown

HIF enters the nucleus where it dimerises and binds to HIF-responsive elements on genes

These genes are required for angiogensesis

Transcription of these genes to form mRNA

Leads to production of VEGF and PDGF

Question 33

What important role does PDGF play?

Answer 33

Important role in tumour progression

Question 34

Formation of vessel via angiogenic sprouting

Answer 34

VEGF selects the tip cell and binds to it

Gradient factors, VEGF and repression molecules cause stalk elongation and tip guidance

Sprout fusion, maturation and perfusion - two tips and stalks fuse

Question 35

What does VEGF bind to?

Answer 35

VEGF receptors

Question 36

Examples of VEGF receptors

Answer 36

VEGF-associated receptor 2

NRP1

Question 37

What type of receptors are VEGF receptors?

Answer 37

Tyrosine kinases

Question 38

What happens when VEGF binds to its receptor?

Answer 38

Association of signalling molecules

Progression of downstream signals

Cascades trigger motility, survival and gene expression

Coordinate the angiogenic response

Question 39

VEGF are a family of secreted proteins - VEGF - A, -B, -C, -D, -E

TRUE or FALSE

Answer 39

TRUE