Vascular endothelium Flashcards
What are the 3 layers of a blood vessel (except capillaries and venules)
- tunica adventitia: vasa vasorum, nerves
- tunica media: smooth muscle cells
- tunica intima: endothelium
What are vasa vasorum?
little blood vessels in the tunica adventitia that feed the vessel wall in larger blood vessels
What is the structure of capillaries and venules?
- endothelial cells/endothelium
- supported by pericytes (mural cells)
- and basement membrane
What are the roles of the microvascular endothelium?
- source of angiocrine factors–> for organ regeneration
- vital barrier between blood and tissues
- tissue homeostasis: controls vascular tone (i.e. vasoconstriction/vasodilation), angiogenesis, permeability, inflammation (anti-/pro-), haemostasis and thrombosis
How do endothelial cells form a flat monolayer?
contact inhibition:
cell junctions come together and signal cells to stop growing, so endothelial cells have a low proliferation rate (except in angiogenesis)
How are endothelial cells heterogeneous?
their function and phenotype depends on their location
–> tissue-specific microvasculature/organotypic
e.g. brain vs kidney (permeability)
What is the result of chronic activation of the endothelium?
- activation causes switch from anti-inflammatory/anti-thrombotic/anti-proliferative –> PRO- those things
- thrombosis, increased permeability, leukocyte recruitment and adhesion, senescence
- –> all contribute to development of atherosclerosis
What factors trigger chronic activation of the endothelium/RISK FACTORS FOR ATHEROSCLEROSIS?
- smoking, air pollutants
- infections
- haemodynamic forces e.g. disturbed blood flow
- oxidative stress
- hypercholesterolaemia
- DM/metabolic syndrome
- hypertension
- sex hormonal imbalance
- inflammation
- ageing
What results in foam cell formation?
phagocytosis of lipids by leukocytes in the subendothelial space
What are the 4 key mechanisms of endothelial dysfunction in the pathogenesis of atherosclerosis?
- leukocyte recruitment
- permeability
- shear stress
- angiogenesis
When and where does recruitment of leukocytes from blood into tissues normally take place?
during inflammation–> leukocytes adhere to endothelium of post-capillary venules and transmigrate into tissues
How does leukocyte recruitment contribute to the development of atherosclerosis?
- leukocytes adhere to the activated endothelium of large arteries–> get stuck in sub endothelial space, as unable to break through various layers of vessel e.g. smooth muscle
- monocytes that have migrated into sub endothelial space (inflammatory environment w/lipids) differentiate into macrophages and then into foam cells
^key event that promotes formation of plaque
How does vascular permeability contribute to the development of atherosclerosis?
- endothelium regulates flux of fluids and molecules to/from blood and tissues
- increased permeability leads to inc. flux of plasma proteins into subendothelial space, which is thick w/ extracellular matrix and proteoglycans
- leaked lipoproteins get oxidised by proteoglycans–> macrophages uptake modified LDL by phagocytosis
- -> foam cells form
Why do atherosclerotic plaques occur preferentially at bifurcations and curvatures in the vascular tree?
the flow patterns and haemodynamic forces are not uniform in the vascular system:
- in straight parts of arteries, blood flow is laminar and wall shear stress is HIGH and directional
- in branches and curvatures, blood flow is disturbed/turbulent w/ nonuniform, irregular distribution of lower shear stress
What are the protective effects of laminar blood flow on the vascular endothelium?
- promotes anti-thrombotic (e.g. thrombomodulin) and anti-inflammatory factors
- promotes endothelial survival
- inhibits smooth muscle cell proliferation
- promotes production of NO (nitric oxide)
