Angiogenesis 1
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- Created by: Rscottqub
- Created on: 09-03-20 13:07
what type of cells line all vessels
endothethial cells - they rarely divide in adult life, but if stimulated they can divide v quickly
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2 processes involved in new blood vessel formaton
1. vasculogenesis 2. angiogensis
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vasculogenesis
occurs during embroygenesis, conversion of angioblasts into endothethial cells. the de novo formation of the vasuclar network
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De Novo
from the beginning
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angiogenesis
formation of vasculature from pre existing vessels, occurs in both embryonic development and post natal life
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when does angiogenesis occur
wound healing, reproduction
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angiogenesis is a highly
regulated process. it is switched on for a short period of time and then switched off
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on switches
angiogenesis stimulating factors
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off switches
inhibitors of angio GFs
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how is angiogenesis switched off generally
the production of more inhibitors than simulators
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pathological angiogeneis
unregulated angio can lead to pathologies
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Degenerative retina diseases
AMD, diabetic retinopathy
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AMD
age related macular degeneration. bleeding into the eye causes new vasculature to form. but new isnt as good as old and still causes leakage into eye
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Diabetic retinopathy
high sugar levels can result in continuous inflammation. again new vessel formation , not as good - leakage into the eye
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athersosclerotic plaques
coronary arteries are normally free from microvessels, except in APs - here they form a capil network - which can lead to haemorrages - blot clot --> heart attack
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endometriosis
high levels of VEGF- A - increased angio. also increased levels of IL4 and angiopoitin 2
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Chrons disease
cause is unknown, thought to perhaps be an autoimmune disease. Increased angio GF expressed
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psoriasis
high levels of angio GFs. hypervasculated lesions where the number of new vessels exceeds the metabolic demands
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cancer
this is an angio dependent process. tumor needs network to receive O2 and nutrients. Also allows the tumor to metastasize. They form this network by releasing angio GFs
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process of angiogensis
1. Angio GF produced 2. GFs released by cells with metabolic demand 3. GFs bind to endo cell receptors 4. receptors activated and release proteases - they degrade the basement membrane of existing vessel
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steps 5-10
5. endo cells proliferate 6. endo cells migrate into interstitial space 7. ECM remodeling 8. Lumen formation 9. fusion of new vessels into loops 10. stabalisation of the new b.membrane
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at which point does blood start to flow
after step 8 /at step 9
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endogenous angio GFs
VEGF, angiopoietin, FGF-2, PDGF. they all stimulate endo cell proliferation
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VEGF
Vascular endothelial growth factor - expressed in many tissues, regulates vascular permeability - which is important for angio initiation
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is it important in embryonic development? how do we know this
yes, the loss of 1 VEGF allele results in cell death - therefore must have a crucial role in embryonic development
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transcription of VEGF is induced by
TNFa and PDGF
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what else can regulate VEGF levels
oxygen tension
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hypoxia
regions of the body deprived of O2
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hypoxic regulation of VEGF
hypoxic tissues can increase O2 received by formation of new vessels by producing VEGF
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VEGF receptors
TRKs - VEGFR1 and VEGFR2 - high affinity receptors on surface of endo. expression is also effected by hypoxia
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angiopoitins
receptors for angiopoitins are expressed in endo cells - Tie 1 and Tie 2 (also TKRs)
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function of angiopoitins
vessel development and maturation
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Tie 2
both angiopoeitin 1+2 bind , but only 1 results in signal transduction and maturation
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Tie 1
poorly understood, thought to be a modulator of Tie 2
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FGF
fibroblast growth factors
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2 types of FGF receptors
1. high affinity TK FGF 2 receptors 2. low affinity heparin sulfate proteoglycans
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whats does FGFR activation trigger
proliferation and migration
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PDGF-BB
homodimer, binds to TKR , stabalises the vasculature
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B. membrane breakdown by proteolysis
for a new capil to form the BM must degrade and invasion of the stroma by the surrounding tissue
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role of stromal cells
tumor cells may secret stromal cell recruitment factors . Stromal cells are and additional source of GFs
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capillary formation + vessel maturation
once the BM has degrade, capillaries are formed by alternate cycles of activation and inhibition of proteolyisis . when suffiencinet vessels have been formed then angio is down regulated and switched off
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Other cards in this set
Card 2
Front
2 processes involved in new blood vessel formaton
Back
1. vasculogenesis 2. angiogensis
Card 3
Front
vasculogenesis
Back
Card 4
Front
De Novo
Back
Card 5
Front
angiogenesis
Back
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