Chapter 10 Angiogenesis
Building the blood vessels
Vasculogenesis: formation of new blood vessels from precursor cells (angioblasts)
Vascular remodelling: adaptation and maturation of (primitive) blood vessels
Arteriogenesis: increase in diameter of already existing arterial vessels
Angiogenesis: formation of new blood vessels from existing blood vessels
Pregnancy/embryogenesis + wound healing + inflammation
Cardiovascular disorders + inflammatory disease + cancer
Endothelial cells – they key players in angiogenesis
Functions of endothelial cells:
1. Transport of molecules over the vessel wall
2. Initation/regulation of the clotting system
3. Selection of the white blood cells forming the leukocyte infiltrate
4. Formation of new blood vessels – angiogenesis
Angiogenesis – a multistep endothelial cell
process
1. Quiescent: normal resting blood vessels
lined by endothelial cells (red) and
covered by supportive cells pericytes
(green)
2. Vessel dilation and pericyte detachment
3. Degradation of matrix and basement
membrane; endothelial cells start to
produce enzymes (matrix
metalloproteases (MMPs)) which degrade
matrix and basement membrane
4. Cellular migration and proliferation of endothelial cells into the direction of the
signal
5. Lumen formation, basement formation and pericyte attachment. Fusion of
blood vessel sprouts and further vessel maturation
Angiogenesis in cancer
Tumors (primary and metastases) require blood vessels to grow and tumor cells
secrete soluble factors to induce angiogenesis
The angiogenic balance: balance between activators and
inhibitors that dictates the angiogenic activity
Dormant tumor; equilibrium between activators and
inhibitors – angiogenesis is not activated
Angiogenic tumor: more activators than inhibitors – angiogenesis is activated
The activators and inhibitors are released once endothelial cells start to degrade the
matrix
Activators: vascular endothelial growth factor (VEGF) and other growth factors
Inhibitors: angiostatin, endostatin, tumstatin, anastellin, platelet factor 4,
thrombospondin1|2
Building the blood vessels
Vasculogenesis: formation of new blood vessels from precursor cells (angioblasts)
Vascular remodelling: adaptation and maturation of (primitive) blood vessels
Arteriogenesis: increase in diameter of already existing arterial vessels
Angiogenesis: formation of new blood vessels from existing blood vessels
Pregnancy/embryogenesis + wound healing + inflammation
Cardiovascular disorders + inflammatory disease + cancer
Endothelial cells – they key players in angiogenesis
Functions of endothelial cells:
1. Transport of molecules over the vessel wall
2. Initation/regulation of the clotting system
3. Selection of the white blood cells forming the leukocyte infiltrate
4. Formation of new blood vessels – angiogenesis
Angiogenesis – a multistep endothelial cell
process
1. Quiescent: normal resting blood vessels
lined by endothelial cells (red) and
covered by supportive cells pericytes
(green)
2. Vessel dilation and pericyte detachment
3. Degradation of matrix and basement
membrane; endothelial cells start to
produce enzymes (matrix
metalloproteases (MMPs)) which degrade
matrix and basement membrane
4. Cellular migration and proliferation of endothelial cells into the direction of the
signal
5. Lumen formation, basement formation and pericyte attachment. Fusion of
blood vessel sprouts and further vessel maturation
Angiogenesis in cancer
Tumors (primary and metastases) require blood vessels to grow and tumor cells
secrete soluble factors to induce angiogenesis
The angiogenic balance: balance between activators and
inhibitors that dictates the angiogenic activity
Dormant tumor; equilibrium between activators and
inhibitors – angiogenesis is not activated
Angiogenic tumor: more activators than inhibitors – angiogenesis is activated
The activators and inhibitors are released once endothelial cells start to degrade the
matrix
Activators: vascular endothelial growth factor (VEGF) and other growth factors
Inhibitors: angiostatin, endostatin, tumstatin, anastellin, platelet factor 4,
thrombospondin1|2
