Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

Pmy2106 > Angiogenisis > Flashcards

Angiogenisis Flashcards

1
Q

What are the 2 processes reprising or got the formation of new blood vessels

A

Vasculogenesis -

Angiogenesis -

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Vasculogensis

A

Differentiation of angioblasts into endotheialcells and the new formation of vascular network.
Occurs during embryogenesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Angiogenesis

A

The formation of vascular spouts from pre exsisting vessels
Results in a highly branched vascular network.
Occurs during development and post natal life.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

When does angiogenesis occur

A

During development
Post natal -
Blood vessel in placenta
Thickening of endometrium
ReSponse to stimulus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are the main on switches of angiogenesis known as

A

Angiogenesis stimulating growth factors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are the main off switches of angiogenesis known as

A

Angiogenesis inhibitors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

How is angiogenesis tirner off

A

The production of more inhibitors than stimuiators

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What eye conditions could unregauktion of angiogenesis lead to

A

Age related macular degeneration
Wet- presecence if immature vascularisation in retina which leak - occulusiom of retina - blindness

Diabetic retinopathy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

How does angiogenesis contribute to atherosclerotic plaque

A

When blood vessels become thickened from atherosclerotic plaque , hypoxemia is stimulated in the local area. This is a stimulus to switch in angiogenesis process .
Thickened bv starts to make fragile micro vessels in order to supply oxygen to the area , this can lead to leakage of these immature vessels - formation of blood clotting , leading to cycle of plaques IN CVD.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Endometriosis

A

Lining of the womb, which normally thickens during menstral cycle, starts to grow outside of the womb. In bad cases , these lesions can cause tubular and ovarian adhesions, which needs removed by surgury.

Elevation in VEGF A and soluble vascular endothelial growth factor receptor 1 and 2 (sVEGFR 1+2)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Crohns disease

A

SVEGFR has been shown to be increased in patients. , increased angiogenesis is also leading to underlying o pathology.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Cancer

A

Cancer is a angiogenesis dependant process . A bowing tumour needs vat vascular network to provide nutrients and oxygen . In addition , new tumour blood vessels provide a way for tumour cells to enter the circulation and metastazie to sdistabt organs.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

How does tumour stimulate angiogenesis

A

After about 2mm inner cells of tumour become starved of oxygen. This is a signal to the cells that they need oxygen
The repsponse is to stimulate angiogenesis
Secretion of gf to stimulate angiogenesis act on endothelial cells of capillary network.
Pridtcuon of new BV , supply oxygen and nutrients ti growing tumour , gets bugger , can develop beyond orginal place of growing cells
Travels through body - metastatic spread

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Multi step process Of angiogenesis

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Key proangiogenic factors

A

Vascular endothelial growth factor (VEGF)
angiopoietin 1
Basic fibroblast growth factor (FGF-2)
Platelet derived growth factor (PDGF)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Main tissues vegf is expressed in

A

Brain
Kidney
Liver
Spleen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What does vegf regulate in the Body

A

Vascular permeability after binding to endothelial cells , important for the initiation of angiogenesis.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

How do you know VEGf plays important role in development of vascular system

A

If you delete even one allele of VEGf the embryo will not survive

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What growth factors and cytokines indice transcription of VEGf

A

PDGF
epidermal growth factor
TNF a and b
Interleukin b

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

How is vegf regulated

A

By tissue oxygen tension - levels of vegf sensitive to oxygen levels of environment

21
Q

Vegf receptors,

A

Vegfr 1+2
Regyaktuon o PEF vegfr regulated by oxygen levels

22
Q

Angiopoeitins

A

Family of proteins . Four types agp 1234

Bund ti tyrosine receptor kinase. 2 molecules of meditator bind together. Causing receptor to dimerise , leading to tyrosine kinase function of this receptor and ibtraceukkar signal transduction downstream of receptor activator.

These receptors - tie 1 and 2 are preferentially expressed on endothelial cells.

23
Q

Basic fgf

A

Basic fibroblast growth factor.

Secreted by
Stem cells
Vascular endothelial cells

Binding to receptor shown to trigger intracellular signalling cascade leading to
Proliferation and migration of endothelial cell
Angiogenesis
Production of proteases
Differentiation

FGF2 again binds ro tyrosi;kinase receptor

24
Q

Platelet derived growth fvactorsn

A

Comproswd of four different polypeptide chains which are inactive in their monomeric form

4 diff Types a b c d

After the polypeptides have been translated they exhibit their effects by dimerising and binding to tyrosine kinase receptor.

Associated with various steps in angiogenesis

Maturation of newly formed vascular network
Proliferation and migration of endothelial cells
Stimulation and activation of endotheialcells and release of proangiogenic factors.

25
What enzymes are required to break down basement men,brand
Urokinase plasminogen activator uPA Matrix metalloproteimase
26
Role of stromal cells
Tumour cells can release many soluble factors such as those that switch on angiogenesis. Other solubke factors recruit stromal cells to tissue micro environment. Recruitment of these tissue stromal cells are also a source of expression of proangiogenic factors. Angiogenesis is become uncontrollably activated and not regulated in a normal fashion
27
How is vascular stabilised in angiogenesis
At leading end , there is continuous cycles or endothelial cells proliferation and remodelling of t(e basement membrane . Part of this process is both release of basement membrane proteins from the endothelial cells and also the release of factors that digest basement membrane. This continues to vascular reaches tissue that stimulates the angiogenesis process At the trailing edge the vascular is matured , one of the most important process here is the recruitment of pericytes and smooth muscle cells ,. Cknrollled by PDGF from new capillaries Once their is sufficient maturation proangiogenic factors down regulated. Endotheialcells go back into resting state.
28
What happens in pathological angiogenis vascular maturation
Angiogenis not switched of. Vascular not properly insulated by Pericytes and smooth muscle cells Leads to leaky irregular sized vessels.
29
5 classes of angiogenic antagonist
Inhibition of proteases (inhinit synthesis of MMP) Inhibitors of endothelial cell migration and proliferation Inhibitors of angiogenic growth factors Inhibitors of matrix proteins on endothelial cell surface Inhibitors with a unique mechanism
30
Types of anti veg f drugs
MONOCLONAL ANTIBODIES DIrected against specific proganiogenic growth factors like VEGf SMALL MOLECULE TYROSINE KINASE INHIBITORS
31
Where do anti VEGf drugs inhinit at
At the level of the growth factor At the level of the growth factor binding to the receptor Level of the receptor transduction pathway once receptor has been activated
32
How do antibody mediated VEGF inhibition work a
Anyubidy has a high affinity for its antigen ( VEGF or VEGFR) this will either neutralise the growth factor or or binds to receotor and inhibits down stream signalling of that receptor Also leads to cytotoxic response in the cell via antibody dependant cell mediated toxicity or complement dependant cytotoxicity
33
Examples of monoclonal antibodies
Ramucirumab Anti VEGf 2 inhibitor Alfibercept Hugh binding affinity Made of extra cellular domains of VEGfr 1 and 2 Fused to constant region of human 1gG1 Binds ti vegf and neutarlisesbut and orecents it from binding to down stream receptor
34
What are protein kinases
Enzymes found in cells that catalyse the transfer of gonna phosphate from atp onto the hydroxyl group on amino acid residue on target protein . Resukts in conformational change in target protein that can reveal a catalytic active domain in target protein and stimulate activation of the target protein.
35
Wheee are RTK relatively conserved and where do they differ
Conserved - tyrosine kinase domain Variability found in the extra cellular domain
36
How does activation of tyrosine kinase domain happen
Ligand binds to RTK receptor dimerise Dimerisation resukts in auto phosphorylation in intracellukar domain of RTK Confirmation change revealing ATP and substrate binding domains of tyrosine kinase domain of RTK
37
How many sub families of NRTKS are there and how are they defined
Nine and defined according to sequins similarities
38
How does activation NRTKs occur
Various interactions with other signalling proteins and confirmation hcnsges like In RTI occur revealing ATP And substrate binding domain of the protein
39
Types of kinase
Serine / threonine kinase Receptor tyrosine kinssses Non receptor tyrosine kinases
40
What do serine / threonine kinases do
Catalyse the phosphorylation of serine / threonine
41
Example of serine threonine kinase and it structure
RAF Enclosed format where the catylytic site is nit accessible to substrate or ATP
42
What happen upon activation of raf
Conformational change that opens up the catyltic domain revealing the ATP and substrate binding domain on the protein
43
Tyrosine kinase inhibitorsn Description
These are membrane permeable organic mole files that diffuse through the membrane bilayer and target the ATP binding site of various kinases causing their inhibition These inhibitors may target various different tk domains suggesting structural similarity and decreased drug specificity
44
Example of two multi kinase inhibitors
Sorafanib Thalidomide
45
Sorafanib
Inhibits ATP binding site of RAF and receptor tk domain of a number of RTK. - multi kinase inhibitors Sorafanib competes with ATP for hydrophobic binding pocket of kinase.
46
Thalidomide
Thalidomide marketed over 400 years ago as mild sensitive and help with morning sickness Limbs didn’t form in baby One thought of this cause is that thilomide inhibits angiogenis Now used as anti angiogenesis therapy Family of drug known as IMid - immunomodulatory drugs with an imide drugs Binds to cereblon protein - substrates come in contact with cereblon and become ibiquitinated and causes degradation of that protein Therefore it has an inhibitory effect on pro ag factors
47
Limitation of anti angiogenic treatments
Prolonged administration of anti angiogenic drugs reduce the micro vascular density within tumour and the and may compromise the delivery of chemo to the tumour cells
48
Macugen
VEGf antagonist Binds to VEGf prevents it from binding to receptor Aptamer - short strand of DNA

Pmy2106 (14 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions