MCM Final - Angiogenesis Flashcards
endothelial cells
single layer of cells that lines vessels
localizes immune system and response to ischemic environment
-important roles
where are vessels derived from? (cell type)
mesoderm
cells in vessels
endothelial cells, basal lamina, connective tissue and smooth muscle, and pericytes
basal membrane in blood vessels
ECM laid down for support and to create barrier
smooth muscle in vessel?
only larger ones, not capillaries
pericyte
extends processes that surround the capillary
vasculogenesis
during embryonic development
-primitive vascular network from endothelial and hemopoetic precursors
angiogenesis
vessel formation during adulthood
-growth by new vessels sprouting from existing ones
during pathology**
angioblast
endothelial cell precursor
VEG-F
released by mesenchymal cells causing vasculogenesis
neovascularization
aka angiogenesis
capillary sprout
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
tip cell
does not divide
has filopodia
begins formation of capillary sprout (from existent endothelium cell)
responds to guidance signals (semaphorins, slits, netrins, ephrins)
stalk cells
follows the tip cell during angiogenesis
actively dividing
-forms a hollow lumen
EPCs
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
Process of Angiogenesis
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
MMPs
matrix metalloproteinases
-cause the degradation of the vessel basement membrane during angiogenesis
plasminogen activator
VEGF-A
vascular endothelial growth factor
acts as paracrine ligand
diffuse and interacts with VEGFR-2 receptor
- downstream signaling pathway - tyrosine kinase receptor
VEGFR-2
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
pro-angiogenic proteins upregulated by VEGF-A?
plasminogen activator
collagenase
don’t worry about these too much - will learn later