Angiogenesis Flashcards
What is the role of VEGF?
VEGF stimulates proliferation and migration of endothelial cells. It also promotes vasodilation via the production of NO.
What is the role of FGF-2? (fibroblast growth factor)
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.
What is the role of PDGF?
PDGF recruits smooth muscle cells to the site.
What is the role of angiogenic growth factor (ANG-1,2)?
Ang-1,2 stabilizes the vessels
What is the role of TGF-beta in angiogenesis?
TGF-beta is the most important growth factor for the development of connective tissue (stimulates fibrosis).
What is the two-hit hypothesis?
That one growth factor will set a cell up for another growth factor at a later stage in the process (making a cell competent).
What is the first step of angiogenesis?
Vasodilation (via NO) and increased permeability
What is the second step?
Separation of pericytes
What is the third step?
Breakdown of membranes via MMP (matrix metalloproteinases)
What is the fourth step?
Migration of endothelial cells
What is the fifth step?
Proliferation of endothelial cells behind the tip cells
What is the sixth step?
Remodeling into capillary tubes
What is the seventh step?
Recruitment of periendothelial cells (pericytes for smaller vessels and smooth muscle for larger vessels).
What is the eighth and last step of angiogenesis?
Suppression of migration and proliferation of endothelial cells and deposition of the basement membrane.
What is the role of NOTCH signaling in angiogenesis?
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.
How does NOTCH prevent excessive angiogenesis and proper spacing at the tip cells?
It suppresses VEGF at the stalk/tip cells.
What stage of the wound healing process is angiogenesis associated with?
Angiogenesis is associated with the proliferative stage of the wound healing process. (8-10 days after the wound)
What are some associated diseases with angiogenesis?
Retinopathy, neoplasia, atherosclerosis, Von-Hippel-Lindau disease.
What is Von-Hippel-Lindau disease?
Highly vascularized tumors in the cerebellum, brain stem, and retina, as well as hemangioblastomas (CNS and kidney cancers).
What causes Von-Hippel-Landau disease?
Deletion of the VHL (tumor suppressor) gene on chromosome 3.
What does the deletion of the VHL gene on chromosome 3 cause?
Constitutive expression of angiogenic growth factor (Ang-1,2)
What leads to limb ischemia in diabetics?
Diabetic patients do not up-regulate VEGF in response to hypoxia.