Vascular Endothelium Flashcards
What are the layers of blood vessels (except capillaries and venules)?
tunica adventitia
tunica media
tunica intima
What is in the tunica adventitia?
vaso vasorum
nerves
What is in the tunica media?
smooth muscle cells
What is in the tunica intima?
endothelium
Capillaries and venules are formed only by _________ supported by some _____ and a _______.
endothelium
pericytes (mural cells)
basement membrane
Capillaries is where what occurs?
exchange of nutrients and oxygen between blood and tissue
Microvascular endothelium promotes?
tissue homeostasis
Damage to the endothelium can cause? List examples
organ dysfunction e.g. ischaemia, chronic inflammatory diseases, cancer, diabetes
Microvascular endothelium is the source of what factors required for tissue homeostasis and organ regeneration?
angiocrine
What does organotypic properties mean?
tissue specific, heterogenous
Endothelial cells lining the vascular system
SA >1000m^2, >100g, v flat, 1-2 µm thick and 10-20 µm in diameter, formed by a monolayer of endothelial cells, one cell deep (contact inhibition)
Describe the proliferation rate of endothelial cells in vivo.
low
What functions of blood vessels and tissues does the endothelium control?
vascular tone angiogenesis haemostasis and thrombosis inflammation permeability
What factors are produced from the endothelial cells for angiogenesis?
matrix products: fibronectin, laminin, collagen, proteoglycans, proteases
growth factors: insulin like GF, transforming GF, colony stim. factor
What factors are produced from the endothelial cells for inflammation?
adhesion molecules: ICAMs, VCAM, selectins
inflammatory mediators: IL1/6/8, leukotrienes, MHCII
What factors are produced from the endothelial cells for vascular tone/permeability?
vasodilators: NO, prostacyclin
vasoconstrictors: ACE, thromboxane A2, leukotrienes, free radicals, endothelin
What antithrombotic factors are produced from the endothelial cells for thrombosis/haemostasis?
prostacyclin, thrombomodulin, antithrombin, plasminogen activator, heparin
What procoagulant factors are produced from the endothelial cells for angiogenesis?
VWF, thromboxane A2, thromboplastin, factor V, platelet activating factor, plasminogen activator inhibitor
factors contributing to atherosclerosis
viruses smoking mechanical stress inflammation hypertension OxLDL high glucose sex hormon imbalance ageing
Endothelial dysfunction in atherosclerosis
increased permeability to lipoproteins and other plasma constituents, up-regulation of leukocyte/endothelial adhesion molecules, migration of leukocytes into the artery wall
Briefly outline pathogenesis of atherosclerosis.
- Endothelial dysfunction in atherosclerosis
- fatty streak formation
- formation of an advanced, complicated lesion of atherosclerosis
What happens during fatty streak formation?
smooth muscle migration, foam cell formation, adherence/aggregation of platelets
What happens during formation of an advanced, complicated lesion of atherosclerosis?
macrophage accumulation
formation of a necrotic core
fibrous cap formation
angiogenesis
Endothelial dysfunction in the pathogenesis of atherosclerosis: mechanisms
leukocyte recruitment,
permeability, shear stress, angiogenesis
Describe the leukocyte adhesion cascade.
capture, rolling + activation, arrest, adhesion, intravascular crawling, paracellular + transcellular transmigration
Recruitment of blood leukocytes into tissues normally takes place during?
inflammation
Leukocytes adhere to the endothelium of ______________ and transmigrate into tissues.
post-capillary venules
compare structure of capillaries and post capillary venules
post-capillary venules have more pericytes
In atherosclerosis, leukocytes adhere to activated endothelium of _______ and get stuck in the subendothelial space
large arteries
_______ migrate into the subendothelial space, differentiate into __________ and become foam cells.
Monocytes
macrophages
Increased permeability results in _____________ through the junctions into the subendothelial space.
leakage of plasma proteins
describe lipoprotein trapping/modification
lipoprotein leak out > bind to proteoglycans > become oxidated > join macrophage to form foam cells
Atherosclerotic plaques occur preferentially at ________ and _________ of the vascular tree
bifurcations and curvatures
Why does atherosclerosis occur at branch points?
flow patterns and hemodynamic forces are not uniform in the vascular system
How does blood flow affect stress?
straight parts > laminar flow > high, directional stress
branches/curvatures > flow disturbed > irregular distribution of low wall shear stress
Laminar blood flow promotes?
anti-thrombotic, anti-inflammatory factors
endothelial survival
Inhibition of SMC proliferation
Nitric oxide (NO) production
Disturbed blood flow promotes?
Thrombosis, inflammation (leukocyte adhesion)
endothelial apoptosis
SMC proliferation
Loss of Nitric oxide (NO) production
List protective effects of nitric oxide (NO) on the vascular endothelium.
vasodilator, reduces platelet activation, inhibits monocyte adhesion, reduces SMC proliferation, reduce release of superoxide radicals, reduces oxidation of LDL cholesterol
define angiogenesis
formation of new vessels by sprouting from existing vessels
outline the cascade of events that leads to angiogenesis
hypoxia > EC receptor binding > activation > proliferation > directional migration > ECM remodelling > tube formation > loop formation > vascular stabilisation
Angiogenesis is essential for?
embryonic development, wound healing, menstrual cycle
pathological angiogenesis promotes?
plaque growth
therapeutic angiogenesis prevents?
damage post ischaemia
