Lecture 1- Intro

Question 1

what is the definition of vasculogenesis

Answer 1

denovo formation of circulatory system

Question 2

what is the definition of angiogenesis

Answer 2

new blood vessels from a pre-existing system

Question 3

what is the definition of lymphangiogenesis

Answer 3

formation of the lymphatic system

Question 4

define an open circulatory system

Answer 4

blood is continuous with intercellular fluid e.g. in fruit flies

Question 5

define a closed circulatory system

Answer 5

some components of the blood never leave blood vessels- found in fish, amphibia, reptiles, birds and mammals

Question 6

what sort of cells are able to form tubes

Answer 6

endothelial, epithelial, lymphoendothelial, muscle, bone

Question 7

describe the anatomy of a blood vessel

Answer 7

lumen surrounded by the endothelial lining surrounded by elastic lamina made of elastin fibres surrounded by smooth muscle surrounded by loose connective tissue

Question 8

how is angiogenesis stimulated

Answer 8

growth signals

Question 9

describe the process of vasculogenesis for forming the heart and first vascular plexus in the embryo

Answer 9

requires in situ differentiation and growth from mesodermal-derived hermangioblasts (vascular stem cells). cells express different markers and become other cells in the blood or blood vessel depending upon which growth factors they encounter. endothelial cells differentiate from angioblasts and express markers and membrane receptors ef PECAM1 and VEGFR2. they migrate towards the endoderm, guided by VEGF-A concentration gradient and form the aortic primordial structure. other cells arrange themselves around these

Question 10

why are cell-cell junctions critical for setting up vascular networks

Answer 10

they ensure correct polarisation of endothelial cells. this is regulated by ephori’s and ephori receptors which are cell surface tyrosine kinases and adhesion molecules.

Question 11

describe the process of forming a vascular tube

Answer 11

there are a number of differenct proposed models including the cord hollowing model and vacuole fusion model

Question 12

describe the mechanism of blood vessel branching

Answer 12

1. endothelial tip cell is selected
2. the tip guide other cells which form the vascular sprout towards a signal such as growth factor signals. this is chemotaxis
3. blood vessels meet up to form a bridge

Question 13

how do VEGFs regulate vasculogenesis

Answer 13

this is soluble ligand which binds growth factor receptors instigating cell signalling pathways incl MAPK pathway which alters gene expression resulting in blood vessel sprouting. The map pathway is under the control of the Ras oncogene

Question 14

other than VEGFs how is vasculogenesis regulated

Answer 14

via angiopoietin growth factors/Tie receptor system and the Ephrin/Eph sytem

Question 15

what size are tumours limited to without blood supply

Answer 15

1-2mm in diameter

Question 16

how do tumours promote blood vessel growth

Answer 16

secretion of VEGF

Question 17

how is VEGF-A synthesis normally regulated

Answer 17

it is regulated by a hypoxia inducible factor. under normal cell conditions HIF-1a is degraded b von hip landau protein and ubiquitination but at low O2 HIF is stabilised by dimerisation of the VHL a and b subunits allowing it to move into the nucleus and promote gene transcription for the production of VEGF-A

Question 18

what is the roll of VEGF-A

Answer 18

angiogenesis and vascular maintenance. loss of even 1 gene causes embryonic lethality

Question 19

what is the role of PIGFs

Answer 19

VEGF associated placental growth factors which are required for angiogenesis and vasculogenesis during ebryogenesis.

Question 20

what is the role of VEGF-B

Answer 20

blood vessel maintenance

Question 21

what is the role of VEGFC + D

Answer 21

required for lymphangiogenesis

Question 22

what is the result of deletion of VEGF receptors

Answer 22

embryonically lethal

Question 23

what is the role of VEGFR1

Answer 23

it has affinity for certain isoforms of VEGF and has a role in cell survival and migration. deletion results in disorganised blood vessels

Question 24

what is the role of VEGFR2

Answer 24

receptor binding results in RTK signalling and downstream MAPK signalling deletion results in no blood vessels

Question 25

what is the role of VEGFR3

Answer 25

deletion results in no blood or lymphatic vessels

Question 26

describe the angiopoietin/Tie system

Answer 26

Ang 1 and 2 are soluble ligands. angel binds tie2 and stimulates tyrosine kinase activity and phosphoryltion whilst angel competes for binding and blocks PTK phosphorylation and activation. Tie NOs lead to leak blood vessels and is thought to recruit cells to the vascular network

Question 27

describe the Eph/EPhrin system

Answer 27

Ephori’s are GPI anchored or TM proteins that act as ligands for ephrin receptors on other cells. ephrin receptors are RTKs and regulate vascular boundaries and determine fate of vascular cell. interaction between ephB2 results in arteries and epb4 results in veins. it joins these up and connects them, controlling cell and tissue bindings as well as regulating angiogenesis

Question 28

what is the difference between the circulatory and lymphatic systems

Answer 28

blood vessels form loops whereas lymphatic systems are branching, open ended networks which drain into blood vessels