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MCM Final Exam > MCM Final - Angiogenesis > Flashcards

MCM Final - Angiogenesis Flashcards

(51 cards)

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0
Q

endothelial cells

A

single layer of cells that lines vessels

localizes immune system and response to ischemic environment
-important roles

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1
Q

where are vessels derived from? (cell type)

A

mesoderm

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2
Q

cells in vessels

A

endothelial cells, basal lamina, connective tissue and smooth muscle, and pericytes

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3
Q

basal membrane in blood vessels

A

ECM laid down for support and to create barrier

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4
Q

smooth muscle in vessel?

A

only larger ones, not capillaries

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5
Q

pericyte

A

extends processes that surround the capillary

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6
Q

vasculogenesis

A

during embryonic development

-primitive vascular network from endothelial and hemopoetic precursors

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7
Q

angiogenesis

A

vessel formation during adulthood

-growth by new vessels sprouting from existing ones

during pathology**

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8
Q

angioblast

A

endothelial cell precursor

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9
Q

VEG-F

A

released by mesenchymal cells causing vasculogenesis

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10
Q

neovascularization

A

aka angiogenesis

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11
Q

capillary sprout

A

originates from existing capillary cell

tip cell - at tip of sprout (not dividing)

stalk cell - follow tip cell, form hollow lumen (actively dividing)

continues growing until reaches another sprout or vessel

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12
Q

tip cell

A

does not divide

has filopodia

begins formation of capillary sprout (from existent endothelium cell)

responds to guidance signals (semaphorins, slits, netrins, ephrins)

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13
Q

stalk cells

A

follows the tip cell during angiogenesis

actively dividing
-forms a hollow lumen

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14
Q

EPCs

A

endothelial precursor cells

migrate from bone marrow
-express VEGFR-2 and VE-cadherin

not necessary for angiogenesis

in ischemic patients - increase in number of EPCs

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15
Q

Process of Angiogenesis

A

1 vasodilation
-nitric oxide (NO) and VEGF dilate the area
2 degradation
-proteolysis of basement membrane (MMPs)
3 migration
-of endothelial cells in direction of growth
-growth factors or inhibitors
4 proliferation
-of endothelial cells
5 maturation
-when make contact with another stalk cell or vessel
-laying down basement membrane, recruiting pericytes, and maybe smooth muscle cells

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16
Q

MMPs

A

matrix metalloproteinases

-cause the degradation of the vessel basement membrane during angiogenesis

plasminogen activator

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17
Q

VEGF-A

A

vascular endothelial growth factor

acts as paracrine ligand

diffuse and interacts with VEGFR-2 receptor

- downstream signaling pathway
- tyrosine kinase receptor
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18
Q

VEGFR-2

A

ligand is VEGF-A

tyrosine kinase receptor

leads to EPC migration from bone marrow, increased vascular permeability, endothelial cell survival and proliferation/motility, upregulate express of pro-angiogenic proteins

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19
Q

pro-angiogenic proteins upregulated by VEGF-A?

A

plasminogen activator
collagenase

don’t worry about these too much - will learn later

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20
Q

what induces VEG-F?

Study These Flashcards
A

hypoxic conditions

- tissue needs more oxygen
- done through Hif1 - expressed due to lack of oxygen
21
Q

Notch receptor in angiogenesis

Study These Flashcards
A

juxtacrine signaling

receptor expressed in stalk cells

allows us to control excessive proliferation of endothelial

decreases cells responsiveness to VEGF

ligand is delta - expressed by the tip cells

22
Q

delta (ligand)

Study These Flashcards
A

secreted from tip cells in response to VEGF activation

bind the notch receptor on the stalk cells

- results in decreased responsive to VEGF
- decrease in branching and proliferation of endothelial stalk cells
23
Q

angiopoietins

Study These Flashcards
A

Ang1 and Ang2 function in opposite ways

24
Ang1
latter steps during maturation of vessel during angiogenesis recruits pericytes and smooth muscles
25
Ang2
antagonist of Ang1 binds same receptor and acts as an inhibitor -continues to allow the endothelial cells and limits the maturation of the vessels during angiogenesis
26
PDGF
platelet-derived growth factor secreted by the endothelial cells and platelet cells PDGFR is the receptor (on pericytes and smooth muscle) release after Ang1 signaling
27
bFGF
basic fibroblast growth factor from endothelial cells and macrophages secreted and stored in the ECM -has affinity for heparin causes induction of mitosis
28
bFGFR
receptor for bFGF - expressed on endothelial cells, fibroblasts, smooth muscle cells, neurons - induces mitosis
29
TGF-beta
transforming growth factor induces VEGF expression -on fibroblasts and endothelium
30
MMPs
matrix metalloproteinases contains zinc diverse family of enzyme any type of tissue remodeling secreted as zymogens (inactive) - because they are dangerous release induced by VEGF, inflammation or damage
31
integrin signaling during angiogenesis
transmembrane receptor integrin binds juxtacrine ligandes - group together and form focal adhesion complexes - leads to intracellular signaling cascase
32
focal adhesion complexes
integrin bound to juxtacrine ligand during angiogenesis
33
thrombospondin-1
inhibitor of angiogenesis upregulated by p53 functions in ending the process of angiogenesis
34
mutation in what protein can promote angiogenesis?
p53
35
Hif-1 alpha
induces the expression of VEGF
36
angiostatin
inhibitor of angiogenesis internal fragment of plasminogen (in circulation) - plasminogen degrades bc of MMPs - releasesfragment of angiostatin inhibits endothelial cell migration and division
37
endostatin
inhibits angiogenesis fragment of collagen released due to MMP activity -inhibits VEGF signaling
38
platelets
fragmented portions of cells protein sack that is released 14 promoters and 12 inhibitors when reaches injured area or clot - regulators released in sequence - pro-angiogenic and later anti-angiogenic sequence - help with the maturation process in tissue
39
down regulation of angiogenesis?
high levels of oxygen leads to degradation of Hif1 no VEGF - no angiogenesis VHL (von hippel lindau) marks Hif1 for degradation
40
VHL
von hippel lindau E3 ubiquitin ligase that marks Hif1 for degradation
41
Von Hippel Lindau Sydrome
mutation in VHL leads to nonfunctioning protein - cannot degrade Hif1 - therefore, constitutively expression of VEGF leads to hemangioblastoma - blood vessel dense tumor
42
hemangioblastoma
blood vessel dense tumor result of von hippel lindau syndrome
43
non-neovascularized tumor
not clinically detectable (except surface lesion) small size slow growth benign
44
neovascularized tumor
tumor has ability to control capillary growth can secrete angiogenic proteins -induce capillary sprout growth
45
two way paracrine exchange in tumors
tumor - angiogenic proteins -vessel growth to tumor endothelial - chemoattractants -tumor migration to blood vessel
46
direct drugs inhibiting angiogenesis?
acting on the endothelial cells to inhibit their response ex./ bevacizumab (avastin)
47
indirect drugs for angiogenesis?
inhibits tumor from secreting pro-angiogenic proteins ex./ trastuzumab (herceptin)
48
Bevacizumab
aka avastin direct drug for inhibiting tumor angiogenesis anti-VEGF antibody used in diabetic retinopathy treatment
49
diabetic retinopathy treatment?
use bevacizumab | -intravitreal injection that causes the inhibition in vascularization of the eye
50
Trastuzumab
(aka herceptin) -indirect breast cancer treatment - Her-2/neu are tyrosine kinases that are overexpressed or mutated in breast cancer - ligand - not known - activation results in pro-angiogenic factor secretion drug acts as antibody antagonist

MCM Final Exam (16 decks)

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