Angiogenesis

Question 1

4 different phases of wound healing

Answer 1

1. coagulation
2. inflammatory
3. proliferative
4. remodeling

Question 1

relating to blood/blood vessels

Answer 1

angio

Question 2

genesis:

Answer 2

beginning

Question 3

angiogenesis essentially develops from what

Answer 3

existing blood vessels

Question 4

2 examples of normal angiogenesis seen in adults

Answer 4

1. uterine lining
2. cut on finger (tissue of finger)

Question 5

patients with _____ have a lack of angiogenesis

Answer 5

diabetes

Question 6

angiogenesis is necessary in 3 circumstances:

Answer 6

1. stroke
2. myocardial infarction
3. incision repair

Question 7

primary cell type involved in angiogenesis

Answer 7

endothelial cell

Question 8

what type of cell is very responsive to hypoxia (low O2 levels)

Answer 8

endothelial cell

Question 9

tight junctions between endothelial cells will be the same or different in different organs

Answer 9

different

Question 10

these are precursors to vascular smooth m. cells and provide cellular support, form structural component to support vessel

Answer 10

pericytes

Question 11

first step in angiogenesis (general)

Answer 11

VEGF binds to receptors on endothelial cells

Question 12

factors involved in step 1 of angiogenesis that bind to VEGFR1 (Flt-1)

Answer 12

PlGF (placental growth factor)
VEGF-A

Question 13

main receptor VEGF-A binds to that causes it to have its primary effect

Answer 13

VEGFR-2 (Flk-1/KDR)

Question 14

factor that binds VEGFR3 and drives lymphatic formation

Answer 14

VEGF-C

Question 15

stimulates proliferation of endothelial cells (this process is selective for EC’s)

Answer 15

VEGF

Question 16

another factor involved in step 1 of angiogenesis that drives proliferation of endothelium

Answer 16

bFGF (basic fibroblast growth factor)

Question 17

ultimately induces gene expression and endothelial cell proliferation that drives angiogenesis

Answer 17

VEGF

Question 18

what causes hypoxia in a wound (edge effect)

Answer 18

bleeding (losing RBC’s that carry O2)

Question 19

what induces angiogenic factor production to get the angiogenesis process started

Answer 19

hypoxia

Question 20

______ drives HIF-alpha and ultimately VEGF expression

Answer 20

hypoxia

Question 21

basement membrane degradation/formation of new matrix is what step in angiogenesis

Answer 21

step 2

Question 22

main drivers of chewing up old matrix and setting down new matrix

Answer 22

MMP’s (matrix metalloproteins)

Question 23

collagenase and degrades collagen I, II, III

Answer 23

MMP-1

Question 24

gelatinase and degrades type IV collagen (packman)

Answer 24

MMP-2

Question 25

gelatinase and degrades type IV and V collagen

Answer 25

MMP-9

Question 26

directional migration and attaching of new matrix is what step in angiogenesis

Answer 26

step 3

Question 27

_____ binds vitronectin, fibronectin, and fibrin (the components of new matrix) + MMP-2

Answer 27

integrins

Question 28

____ highly expressed on ECs exposed to VEGF and bFGF

Answer 28

avB3

Question 29

factors used in step 4 of angiogenesis (blood vessel differentiation and stabilization)

Answer 29

Ang-1 and 2 Ephrins

Question 30

factor used for stabilization of angiogenic vessel and has preference for binding of Tie2/Tie2 homodimer

Answer 30

Ang-1

Question 31

released in step 4 to help vessel form a tube

Answer 31

Ang-1

Question 32

natural inhibitor of Ang-1 (released when Ang-1 no longer needed)

Answer 32

Ang-2

Question 33

factor used in loop formation and differentiation of artery or vein

Answer 33

Ephrin-B

Question 33

receptor Ephrin binds to

Answer 33

EphB

Question 34

expressed on arterial cells

Answer 34

Ephrin B

Question 35

expressed on venous cells

Answer 35

EphB

Question 36

factor that recruits pericytes in last step (pericytes used for vascular stabilization)

Answer 36

Platelet derived growth factor (PDGF)

Question 37

what happens when vessel is stabilized

Answer 37

blood flow restored; hypoxia goes away

Question 38

excessive angiogenesis due to severe hypoxia is seen in diabetic patients and can ultimately lead to vision loss

Answer 38

diabetic retinopathy

Question 39

if you cut off blood supply to tumor what can happen

Answer 39

kill the tumor

Question 40

compared to normal angiogenesis and normal vessels, what are tumor vessels like

Answer 40

tortuous (no structure) leaky vessels (opposite of normal and stable)

Question 41

cancer cells allow tumor to survive by recruiting what

Answer 41

new blood vessels and feeding itself

Question 42

-mab that neutralizes VEGF; used for colorectal cancer

Answer 42

Bevacizumab (Avastin)

Question 43

-nib that inhibits epidermal growth factor receptor so no VEGF is made

Answer 43

Gefitinib

Question 44

-nib that is a VEGF receptor inhibitor; used for RCC and GIST

Answer 44

Sunitinib

Question 45

in early stage treatment with bevacizumab, what happens

Answer 45

it actually stabilizes vessel and allows another drug to be administered and go to tumor and kill it

Question 46

drug that inhibits angiogenesis; inhibits NFkB and promotes apoptosis; SE=sedation; used for multiple myeloma

Answer 46

Thalidomide