Vascular endothelium Flashcards
what is the basic structure of blood vessels?
- 3 layers:
- Tunica adventitia
- Tunica media
- Tunica intima
- Capillaries and venules formed only by endothelium.
what are capillaries and venules supported by?
some mural cells (pericytes) and basement membrane
what is in the tunica adentitia?
vasa vasorum
nerves
what is in the tunica media?
smooth muscle cells
external elastic membrane
what is in the tunica intima?
endothelium
internal elastic membrane
lamina propria (smooth muscle and connective tissue)
what do capillaries do?
exchange nutrients and oxygen between blood tissues?
what does microvasculature endothelium promote?
tissue homeostasis
sources angiocrine factors- maintenance tissue homeostasis and organ regeneration
what can damage to microvasculature endothelium cause?
organ dysfunction
- Ischaemia
- Chronic inflammatory diseases
- Cancer
- Diabetes
- Atherosclerosis
what is the heterogeneity of blood vessels?
not all blood vessels are the same
there is vascular and endothelial heterogeneity
endothelial cells and microvasculatue have organotypic (tissue-specific) properties and expression profiles
function and phenotype depends on location
what is the use of endothelial cells?
barrier separating blood from tissues
regulate essential functions of blood vessels
what is the composition of endothelial cells?
- Very extensive, surface area >100m2
- Flat- 1-2um thick and 10-20um diameter
- Formed by a monolayer of endothelial cells, one cell deep (contact inhibition)
- long life and low proliferation rate
what is contact inhibition?
2 cells form a junction results in cell inhibiting growth
only allows growth in 2 directions
done only by endothelial and epithelial cells
what are the main functions of resting epithelium?
anti-inflammatory
anti-thrombotic
anti-proliferative
what are the actions of activated endothelium?
pro-inflammatory
pro-thrombotic
pro-angiogenic
leukocyte recruitment
increases permeability
this all contributes to atherosclerotic profile
what can cause an activated endothelium?
mechanical stress
inflammation
high BP
OxLDL
high glucose
viruses
smoking
what is the pathogenesis of atherosclerosis?
- endothelial dysfunction
- fatty steak formation
- formation of an advanced, complicated lesion of atherosclerosis
what happens during endothelial dysfunction?
increase in endothelial permeability and endothelial adhesion
leukocyte migration and adhesion
what happens during fatty-streak formation?
smooth muscle migration
T-cell activation
adherence and aggregation of platelets
adherence and entry of leukocytes
causes foam cell formation
what happens during formation of an advanced, complicated lesion?
macrophage accumulation
angiogenesis
formation of a necrotic core with fibrous cap
what are the triggers for atherogenesis?
what is the overall atherosclerosis pathogenesis mechanisms?
- Leukocyte recruitment
- Permeability
- Sheer stress
- Angiogenesis
what happens during leukocyte recruitment?
- recruitment of blood leukocytes into tissue takes place during inflammation
- Leukocytes adhere to endothelium of post-capillary venules and transmigrate into tissues
In atherosclerosis:
- Leukocytes adhere to activated endothelium of large arteries
- Get stuck in subendothelial space
- Monocytes migrate into subendothelial space
- Differentiate into macrophages to become foam cells
what are capillaries?
endothelial cells surrounded by basement membrane and pericapillary cells (pericytes)
what is the difference between capillary and post-capillary venule?
a structure similar to capillaries but more pericytes
how does permeability affect atherosclerosis?
- Endothelium regulates flux of fluids and molecules from blood to tissue and vice versa
- Increased permeability= leakage plasma proteins through junctions into the subendothelial space
- Lipoproteins go through leaky junction and bind to proteoglycans
- Get oxidated in subendothelial space
- Microphages enter and combine with oxidised lipoproteins to form foam cells à early plaque formation
how does sheer stress contribute to atherosclerosis?
- Atherosclerosis occurs preferentially at bifurcations and curvatures of vascular tree
- Flow patterns and hemodynamic forces are not uniform in the vascular system
- Laminar blood flow= straight parts of arterial tree à wall sheer stress high and directional
- Disturbed (turbulent) blood flow= branches and curvature à non uniform and irregular distribution of low wall shear stress à chronic endothelial activation
what are the properties of laminar blood flow?
anti-thrombotic
anti-inflammatory
endothelial survival
inhibition of SMC proliferation
Nitric oxide production
what does disturbed blood flow promote?
thrombosis
inflammation (leukocyte adhesion)
endothelial apoptosis
SMC proliferation
loss nitric oxide production
what are the effects of nitric oxide of the vascular endothelium?
NO is protective and essential for health of cardiovascular system
reduces oxidation of LDL cholesterol (major component in plaque)
dilates blood vessels
reduces platelet activation
inhibits monocyte adhesion
reduces proliferation of SMC in vessel wall
reduces the release of superoxide radicals
what is angiogenesis?
formation of new vessels by sprouting from existing vessels
what can angiogenesis be initiated by?
signalling promoted by hypoxia
what is angiogenesis essential for?
embryonic development
menstrual cycle
wound healing
what is the role of angiogenesis in cardiovascular disease?
good and bad
promotes plaque growth
therapeutic angiogenesis promotes damage post ischemia
( induction of angiogenesis downstream of a plaque= revascularize and prevent loss of tissue)
what is the role of thrombosis and coagulopathy in COVID19 patients?
SARS-CoV2 infection-> cytokine store -> endothelial activation -> procoagulant switch
venous and arterial thrombi frequent -> points to endothelial role
coagulopathy (increase D-dimers, fibrinogen) correlated with poor prognosis
anti-thrombotic therapy recommended in all hospitalised patients
