Angiogenesis Flashcards
What are the two general ways in which heparin facilitates angiogenesis?
- It enhances capillary endothelial cell movement.
2. It enhances the effect of certain endothelial growth factors
Why is heparin present near sites of angiogenesis?
Because there is frequently inflammation, and thus mast cells. The mast cells contain the heparin.
What is the previously unknown function of heparin that allows it to act as a regulator of angiogenesis?
It binds the endothelial growth factors needed.
What is the major growth factor that regulates angiogenesis/
VEGF
What are the major stimuli of angeiogenesis?
VEGF
Hypoxia
PDGF
Angiopoietins
When does angiogenesis occur?
Growth and differentiation Wound repair Endometrial and placental growth Tumor Growth Retinopathies
What are the steps of capillary formation?
Angiogenic signals are present. Endothelial cells degrade the vascular basement membrane by MMPs. Endothelial cells migrate, forming tip cells, that migrate toward the stimulus. Cell proilferation forms a lumen. The lumen extends toward angiogenic signals. The sprout fuse togther.
What does paracrine mean?
Secretion of factors (such as VEGF) that affect local tissues
What are the growth factors used in neovascularization
VEGF, PDGF, EGF
What immune system is cell is commonly found in sites of neovascul.?
Mast Cells
What chemical do mast cells release that plays a key role in neovascul.?
Heparin
How does heparin assist in neovascul.?
Heparin has high affinity binding receptors for VEGF. Heparin also binds to endothelial cells, allow the VEGF to have a prolonged effect in the area.
What is the difference between angiogenesis and arteriogenesis?
Angiogenesis is capillary sprouting, resulting in higher capillary density.
Arteriogenesis is rapid proliferation of collateral arteries.
What are two strategies for inhibiting pathologic angiogenesis?
Inhibition of tumor endothelial proliferation
Vascular normalization
What is angiogenic switch?
Angiogenesis consists of a balance of positive and negative signals. Tumors, once they begin to experience hypoxia, switch the producing more positive signals (such as VEGF) to allow continued existence.
What is refractoriness?
The tumor gene becomes resistant to anti-VEGF therapy
What is the role of transcription factors in pro-angiogenesis?
During hypoxia, HIF stabilization and transactivation of the promoters of target genes such as VEGF. HIF inhibitino could be a new way of anti-angiogenic therapy.
How does hypoxia inducible factor work?
Hypoxia activates HIFs, which upregulate expression of VEGF gene.
Why is the treatment with anti-VEGF therapies sometimes refractory?
I dont know…
What is the role of guidance signals in angiogenesis?
They signal to the tip cell of the growing capillaries where to go.
What is the evidence that cancer grwoth is angiogenesis-dependent?
When cancers are grown extracellularly, they did not stay alive. In contrast, when put into mice, they lived because they grew oxygen-drawing vessels.
What is bevacizumab?
A monoclonal antibody directed against VEGF .
What is the paradox of vascular normalization that makes combination therapy of VEGF blockade and chemotherapy more effective?
VEGF blockade results in temporary normalization of tumor vasculature because it selectively prunes poorly formed vessels, allowing a return to normal bp in well-formed tumor vessels. This, then allows the chemotherapy to be more effectively delivered to the tumor.
What is the drawback of using anti-VEGF therapy on its own?
When drug therapy is stopped, revascularization occurs rapidly using skeletal remains of previously vessels.
Why is HIF inhibition a difficult process to address?
The HIF stabilization is very intact. Also, there is currently no known therapeutic agent that inhibits their stabilization.
What are TKIs?
Tyrosine Kinase Inhibitors that selectively inhigibt TK domains of EGFR.
Why are TKIs second-line therapies?
I don’t know
