The Endothelium Flashcards
What is endothelial heterogeneity?
The endothelial cell is an output-input device, causes response to different surroundings, environments and changes by surrounding to biochemical and mechanical changes.
What are the key physiological functions of the endothelium?
De novo blood vessel network formation New blood vessel sprouting (angiogenesis) Vascular homeostasis Blood clotting Disease related dysfunctions
What are the key adhesive functions of the endothelium
- Provides an intracellular barrier
- Regulates movement of molecules
- Regulates the movement of cells
- Barrier function can regulate angiogenesis and vasculogenesis
What must be controlled in angiogenesis?
Dilation - constriction
Growth inhibition - growth promoters
Antithrombosis - prothrombosis
anti-inflammation - pro-inflammation
What could stimulate angiogenesis?
Low oxygen or hypoxia
Low oxygen in tumours
What stimulates new blood vessels sprouting?
VEGF-A, binds to cognate receptors on the endothelium
What can we now target in fighting tumours?
Receptors for communication, growth factors and signalling circuits.
What is angiogenesis dependent on?
HIF-1 activity, sensitive to oxygen levels, can be stabilised when the oxygen level drops.
What does HIF-1 regulate?
Expression of VGF-A
What do blood vessel sprouts express?
DII4
What do stalk cells express?
Notch and VEGFR2
What does notch signalling do?
Negatively modulates angiogenesis
What does VEGFR2 do?
Positively modulates angiogenesis
What is atherosclerosis?
Plaques or lesions in the coronary arteries causing MI
What are critical in atherosclerosis?
Endothelium-leukocyte interactions
How do leukocytes contribute to atherosclerosis?
monocytes differentiate into macrophages which binds accumulated modified LDLs which become foam cells that die
What causes a heart attack?
Platelets rushing to the artery where the lesion is
what does nitric oxide do?
Role in vascular smooth muscle relaxation
Blocks leukocyte adhesion
Blocks platelet aggregation
What is endothelial stem cell therapy?
Reform the vascular tube such as the coronary artery after a heart attack
What is KSHV?
Linked to HIV, infects endothelial cells and promotes endothelial growth and immortalisation
Forms metastatic tumours
How does KSHV transform endothelial cells?
GPCR blocks cell death, elevates signalling of pro-survival/proliferative growth factors
