Chapter 12 Flashcards
Define angiogenesis
The growth of new vessels from larger pre-existing vessels. It plays an nb role in cancer progression.
What is the precursor cells of the endothelial cell?
Hemangioblasts.
Define vasculogenesis (different than angiogenesis)
de novo formation of a primitive vascular network.
Name and describe the 4 steps of angiogenesis
1) vasodilation and vascular permeability.
occurs primarily in response to NO which upregulates VEGF. Increased vascular permeability leads to plasma proteins leaving the vessels to lay a new matrix on which the endothelial cells can sprout and spread on to.
2) basement membrane degradation.
needed for cells to migrate into extracellular space. MMPs are nb in this step, also for release of GFs from the ECM, such as bFGF, VEGF and IGF-1.
3) endothelial cell proliferation and migration.
tubules first form as cords lacking a lumen. Then VEGF and angiopoietins are nb for lumen formation, support cell recruitment and vessel formation. TSP-1 inhibits lumen formation.
4) support cell recruitment and vessel fusion.
mature bvs require recruitment of support cells such as pericytes and smooth m cells (for small and large vessels respectively). Final stages of new capillary growth where vessels fuse to form closed loops and deliver circulation to newly vascularized areas (this latter part is poorly understood).
What % of endothelial cells in the normal adult are undergoing cell %? (1%, 0.1%, 0.01%)
Name 2 tissue states and 1 normal organ in which angiogenesis is commonly found.
0.01%
Female repro organs. Wound healing, growing tissues
What 2 growth factors are very important in wound healing? Hypoxia leads to increased expression of _____.
FGF 1 and 2
VEGF
Describe alpha V beta 3.
Specifically what type of molecule is it?
What is its role in angiogenesis?
Its an integrin.
Nb for allowing endothelial cell migration into fibrin/fibrinogen clot
There are ___ members of the VEGF family whose effects are primarily mediated by ___ different receptors. List which ligands bind which receptor.
5
A - binds 1 + 2 + heparin sulfate prots of ECM B - binds 1 + neuropilin-1 C - mostly 3 but also 2 D - 2 + 3 E - 2
Name the VEGF receptors and their alternate names.
What type of receptor are they?
Where are they normally expressed?
VEGFR-1 (Flt-1)
VEGFR-2 (Flk-1)
VEGFR-3 (Flt-4)
Tyrosine kinases
VEGFR 1 and 2 - endothelial cells
VEGFR 3 - lymphatics
Describe angiopoietins - what is function, how many of them are there, etc?
What are their receptors?
A family of ligands for the Tie family of receptors. They are RTKs that are primarily expressed in endothelial cells altho they may also be found on endothelial precursor cells.
Ang 1-4 all bind to Tie 2 (not Tie 1)
The angiopoietins are not mitogenic but regulate other cell processes such as cell migration, cell survival and tubule formation
What type of receptors are ephrins? What is their normal function?
Ephrins = RTKs
Involved in the differentiation of venous vs arteriole development
At what distance from BVs can you find viable cells?
100-200 micrometers
Describe angiogenic switch?
disruption of the balance bt pro and anti-angiogenic factors can lead to the start of angiogenesis.
Describe tumor BVs. ie How doe they differ from normal bvs? Where do new cells for making tumor BVs come from?
tortuous, dilated, irregular shape
dead ended and leaky
tumor cells can be a part of the vessel wall
new cells can be recruited from endothelial precursors from bm
Name 3-5 GFs that upregulate angiogenesis.
VEGF bFGF IL-8 placental GF TGF-beta
