Angiogenesis

Question 1

What is the role of VEGF?

Answer 1

VEGF stimulates proliferation and migration of endothelial cells. It also promotes vasodilation via the production of NO.

Question 2

What is the role of FGF-2? (fibroblast growth factor)

Answer 2

FGF-2 stimulates the proliferation of endothelial cells (physical organization of endothelial cells into tube-like structures) and also promotes migration of macrophages and fibroblasts to the site.

Question 3

What is the role of PDGF?

Answer 3

PDGF recruits smooth muscle cells to the site.

Question 4

What is the role of angiogenic growth factor (ANG-1,2)?

Answer 4

Ang-1,2 stabilizes the vessels

Question 5

What is the role of TGF-beta in angiogenesis?

Answer 5

TGF-beta is the most important growth factor for the development of connective tissue (stimulates fibrosis).

Question 6

What is the two-hit hypothesis?

Answer 6

That one growth factor will set a cell up for another growth factor at a later stage in the process (making a cell competent).

Question 7

What is the first step of angiogenesis?

Answer 7

Vasodilation (via NO) and increased permeability

Question 8

What is the second step?

Answer 8

Separation of pericytes

Question 9

What is the third step?

Answer 9

Breakdown of membranes via MMP (matrix metalloproteinases)

Question 10

What is the fourth step?

Answer 10

Migration of endothelial cells

Question 11

What is the fifth step?

Answer 11

Proliferation of endothelial cells behind the tip cells

Question 12

What is the sixth step?

Answer 12

Remodeling into capillary tubes

Question 13

What is the seventh step?

Answer 13

Recruitment of periendothelial cells (pericytes for smaller vessels and smooth muscle for larger vessels).

Question 14

What is the eighth and last step of angiogenesis?

Answer 14

Suppression of migration and proliferation of endothelial cells and deposition of the basement membrane.

Question 15

What is the role of NOTCH signaling in angiogenesis?

Answer 15

NOTCH allows for proper spacing between blood vessels. More specifically it promotes proper signaling for branching and sprouting of new pathways and prevents excessive angiogenesis at the stalk/tip cells.

Question 16

How does NOTCH prevent excessive angiogenesis and proper spacing at the tip cells?

Answer 16

It suppresses VEGF at the stalk/tip cells.

Question 17

What stage of the wound healing process is angiogenesis associated with?

Answer 17

Angiogenesis is associated with the proliferative stage of the wound healing process. (8-10 days after the wound)

Question 18

What are some associated diseases with angiogenesis?

Answer 18

Retinopathy, neoplasia, atherosclerosis, Von-Hippel-Lindau disease.

Question 19

What is Von-Hippel-Lindau disease?

Answer 19

Highly vascularized tumors in the cerebellum, brain stem, and retina, as well as hemangioblastomas (CNS and kidney cancers).

Question 20

What causes Von-Hippel-Landau disease?

Answer 20

Deletion of the VHL (tumor suppressor) gene on chromosome 3.

Question 21

What does the deletion of the VHL gene on chromosome 3 cause?

Answer 21

Constitutive expression of angiogenic growth factor (Ang-1,2)

Question 22

What leads to limb ischemia in diabetics?

Answer 22

Diabetic patients do not up-regulate VEGF in response to hypoxia.