Angiogenesis Flashcards
4 different phases of wound healing
- coagulation
- inflammatory
- proliferative
- remodeling
relating to blood/blood vessels
angio
genesis:
beginning
angiogenesis essentially develops from what
existing blood vessels
2 examples of normal angiogenesis seen in adults
- uterine lining
- cut on finger (tissue of finger)
patients with _____ have a lack of angiogenesis
diabetes
angiogenesis is necessary in 3 circumstances:
- stroke
- myocardial infarction
- incision repair
primary cell type involved in angiogenesis
endothelial cell
what type of cell is very responsive to hypoxia (low O2 levels)
endothelial cell
tight junctions between endothelial cells will be the same or different in different organs
different
these are precursors to vascular smooth m. cells and provide cellular support, form structural component to support vessel
pericytes
first step in angiogenesis (general)
VEGF binds to receptors on endothelial cells
factors involved in step 1 of angiogenesis that bind to VEGFR1 (Flt-1)
PlGF (placental growth factor)
VEGF-A
main receptor VEGF-A binds to that causes it to have its primary effect
VEGFR-2 (Flk-1/KDR)
factor that binds VEGFR3 and drives lymphatic formation
VEGF-C
stimulates proliferation of endothelial cells (this process is selective for EC’s)
VEGF
another factor involved in step 1 of angiogenesis that drives proliferation of endothelium
bFGF (basic fibroblast growth factor)
ultimately induces gene expression and endothelial cell proliferation that drives angiogenesis
VEGF
what causes hypoxia in a wound (edge effect)
bleeding (losing RBC’s that carry O2)
what induces angiogenic factor production to get the angiogenesis process started
hypoxia
______ drives HIF-alpha and ultimately VEGF expression
hypoxia
basement membrane degradation/formation of new matrix is what step in angiogenesis
step 2
main drivers of chewing up old matrix and setting down new matrix
MMP’s (matrix metalloproteins)
collagenase and degrades collagen I, II, III
MMP-1
gelatinase and degrades type IV collagen (packman)
MMP-2
gelatinase and degrades type IV and V collagen
MMP-9
directional migration and attaching of new matrix is what step in angiogenesis
step 3
_____ binds vitronectin, fibronectin, and fibrin (the components of new matrix) + MMP-2
integrins
____ highly expressed on ECs exposed to VEGF and bFGF
avB3
factors used in step 4 of angiogenesis (blood vessel differentiation and stabilization)
Ang-1 and 2
Ephrins
factor used for stabilization of angiogenic vessel and has preference for binding of Tie2/Tie2 homodimer
Ang-1
released in step 4 to help vessel form a tube
Ang-1
natural inhibitor of Ang-1 (released when Ang-1 no longer needed)
Ang-2
factor used in loop formation and differentiation of artery or vein
Ephrin-B
receptor Ephrin binds to
EphB
expressed on arterial cells
Ephrin B
expressed on venous cells
EphB
factor that recruits pericytes in last step (pericytes used for vascular stabilization)
Platelet derived growth factor (PDGF)
what happens when vessel is stabilized
blood flow restored; hypoxia goes away
excessive angiogenesis due to severe hypoxia is seen in diabetic patients and can ultimately lead to vision loss
diabetic retinopathy
if you cut off blood supply to tumor what can happen
kill the tumor
compared to normal angiogenesis and normal vessels, what are tumor vessels like
tortuous (no structure)
leaky vessels
(opposite of normal and stable)
cancer cells allow tumor to survive by recruiting what
new blood vessels and feeding itself
-mab that neutralizes VEGF; used for colorectal cancer
Bevacizumab (Avastin)
-nib that inhibits epidermal growth factor receptor so no VEGF is made
Gefitinib
-nib that is a VEGF receptor inhibitor; used for RCC and GIST
Sunitinib
in early stage treatment with bevacizumab, what happens
it actually stabilizes vessel and allows another drug to be administered and go to tumor and kill it
drug that inhibits angiogenesis; inhibits NFkB and promotes apoptosis; SE=sedation; used for multiple myeloma
Thalidomide
