Angiogenesis Flashcards Preview

FPP Weeks 1 & 2 > Angiogenesis > Flashcards

Flashcards in Angiogenesis Deck (17)
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1
Q

What is angiogenesis versus vasculogenesis?

A
  1. Angiogenesis - Branching of existing vessels
  2. Vasculogenesis - Creation of brand new vessels from scratch
2
Q

Steps for angiogenesis

A
  1. Growth factor stimulation leads to endothelial detachment
  2. Stalk cell serves as root for new endothelial cell growth (sprout)
  3. Tip cells proliferate out from stalk cell to form new endothelium
3
Q

What are the two types of cell necessary for making up a blood vessel?

A
  1. Endothelial cell - Vessel boundary
  2. Smooth muscle - Wraps around the endothelial cells for vessel tone
4
Q

Role of hypoxia in angiogenesis

A
  • Tumor needs nutrients and oxygen to increase biomass
  • Initially tumor will be in a hypoxic state while trying to proliferate
  • EGF pathway stimulates VEGF generation leading to angiogenesis
5
Q

Why do tumors need vascularization?

A
  1. Oxygen
  2. Nutrients
  3. Removal of waste
  4. Prevent acidic environment
6
Q

How does the organization of tumor vasculature compare to standard vasculature?

A
  • Standard: Very organized, straight capillary beds
  • Tumor: Chaotic, leaky
7
Q

What are potential benefits of having leaky vaculature/lymphatics for a tumor?

A

Provides opportunities for tumors to metastasize, lymphatic leaks allow for decompression of pressure

8
Q

What is the angiogenic switch?

A
  • Capillary development in a tumor has delayed evelopment and only a small fraction of hyperplastic islets actually develop agiogenic islets
  • Believed to be thought of due to matrix metalloprotease-9 activation to stimulate VEGF
9
Q

What is the homeostatic model of angiogenesis?

A
  • Prinicple that angiogenesis is a balance between activating and inhibition factors
  • Activators: VEGF-A, VEGF-B/C, FGF1, FGF2, etc.
  • Inhibitors: Thrombospondin-1,2, Interferon A/B, Angiostatin, Endostatin, Collagen IV Fragments etc.
10
Q

What is VEGF?

A
  • Discovered as a potent vascular permeability factor, 50,000 times more potent than histamine
  • Plays roles in cell proliferation, vascular permeability, cell migration, remodeling, kinase activty and vasculogenesis/angiogenesis
11
Q

What are the different types of VEGF receptors?

A
  1. VEGFR2 - Primary cascade that is best studied
  2. VEGFR3 - Major role in vasculogenesis/lymphanogenesis
  3. VEGFR1 - Least understood, purpose not determined yet
12
Q

What is Notch?

A
  • Transmembrane protein used for cell-cell messaging
  • Extracellular domain is cleaved which causes intracellular entry
13
Q

What are advantages of anti-angiogenic therapy?

A
  1. Targeting a genetically stable population (endothelial cells) instead of a genetically unstable one (tumor cells)
  2. Therapy involves naturally occurring preins in the body - High tolerance/less side effects
  3. Easy accessibility for drugs - Circulatory system
  4. Target metastasis at origin
14
Q

What are some different strategies to target VEGF?

A
  1. Anti-VEGF antibodies
  2. Soluble VEGF receptors - Higher affinity than VEGF Ab
  3. Aptamers - Small molecule VEGF inhibitors, horribly toxic
15
Q

What other disease are anti-VEGF antibodies used to treat now?

A

Wet Macular Degeneration

16
Q

What is a common combination target with VEGF?

A
  • Smooth muscle (pericyte) targeting via PDGF receptors
  • Increases susceptibity to VEGF-R inhibition
17
Q

What are mechanisms of resistance to anti-angiogenic therapy?

A