CVR Vascular Endothelium - in health and disease Flashcards
layers of blood vessels (outside to inside)
- tunica adventitia
- tunica media
- tunica intima
what travels in the tunica adventitia?
vasa vasorum
nerves
what forms the tunica media?
smooth muscle cells
whatforms the tunica intima?
endothelium
what vessel types are formed only by endothelial cells?
- capillaries
2. venules
which cells support the endothelial cells that make up capillaries/venules?
pericytes (mural cells)
microvascular endothelium promotes what?
tissue homeostasis
What is the microvascular endothelium the source of and what is their role?
angiocrine factors
Required for tissue homeostasis and organ regeneration
what diseases does dysfunctional endothelium contribute to? (4)
- ischaemia
- chronic inflammatory diseases
- cancer
- diabetes
what contributes to vascular and endothelial heterogeneity?
endothelial cells and microvasculature have organotypic (tissue specific) properties and expression profiles
what is contact inhibition?
when two cells come together, causing them to stop growing
do endothelial cells have a long life?
yes.
And low proliferation rate (unless new vessels required: angiogenesis)
what is the function of endothelial cells?
regulate essential functions of blood vessels
What are the essential functions of the endothelium? (5)
- angiogenesis
- haemostasis and thrombosis
- inflammation
- permeability
- vascular tone
What are factors that lead to an activated endothelium (7)
- mechanical stress
- inflammation
- viruses
- smoking
- high glucose
- oxidised LDL
- high blood pressure
response to injury model of artherosclerosis
- Endothelial dysfunction results in endothelial activation
- endothelial permeability increases, leukocyte migration increases, leukocyte adhesion increases
- leads to foam cell formation
- fatty streak formation occurs
- macrophage accumulation, formation of necrotic core and angiogenesis occur - formation of an advanced, complicated lesion of atherosclerosis
stages of leucocyte adhesion cascade during inflammation of post-capillary venules (5)
- capture
- activation
rolling, slow rolling, arrest - adhesion strengthening, spreading
- intravascular crawling
- paracellular and transcellular transmigration
why is the stages of leucocyte adhesion different in atherosclerosis to what happens in post-capillary venules?
- leukocytes are adhering to activated endothelial cells of large arteries and get stuck in the subendothelial space
what happens to leucocytes stuck in the subendothelial space?
monocytes differentiate into macrophages and become foam cells
what leaks through junctions if endothelial cell permeability increases?
plasma proteins
stages of lipoprotein trapping
leading to fatty streak formation
- endothelial cells are leaky
- lipoproteins leak from vessel
- lipoproteins get oxidised by proteoglycans
- macrophages engulf these oxidised lipoproteins -> forming foam cells
why does artherosclerosis occur preferentially at bifurcation and curvatures of the vascular tree?
- the flow patterns and haemodynamic forces are not uniform in the vascular system
what type of blood flow occurs in the straight parts of the arterial tree?
laminar - wall shear stress is high and directional
what type of blood flow occurs in the branched parts of the arterial tree?
turbulent flow - non uniform and irregular distribution of low wall shear stress
what does laminar blood flow promote? (4)
- anti-thrombotic and anti-inflammatory factors
- endothelial survival
- inhibition of SMC proliferation
- nitric oxide production
What does disturbed blood flow promote?
Thrombosis,inflammation
Endothelial apoptosis
SMC proliferation
Loss of Nitric oxide production
protective effects of nitric oxide (6)
- reduced oxidation of LDL cholesterol (major component of plaque)
- reduces release of superoxide radicals
- dilates blood vessels
- Reduces platelet activation
- inhibits monocyte adhesion
- reduces proliferation of smooth muscle cells in the vessel
what physiological processes is angiogenesis necessary for? (3)
- embryonic development
- wound healing
- menstrual cycle
What are two other important roles of angiogenesis?
Promotes plaque growth
Therapeutic angiogenesis prevents damage post- ischaemia
stages of endothelial involvement with SARS-CoV2 infection
SARS-COV2 infection -> cytokine storm -> endothelial activation -> procoagulant switch (endothelium loses ability to be anticoagulant)
types of macrophage scavenger receptors
A and B
how is arterial Ox-LDL useful?
safe clearance,
reverse cholesterol transport
What is the main host receptor in covid?
ACE2 - not on endothelial cells, but epithelial cells
Where do the majority of endothelial cells reside?
capillaries
Physiologically, in which vessels does leukocyte transmigration occur?
In post-capillary venules
Same as capillaries but with more pericytes
Which processes promotes early development of atherosclerotic plaques (3)?
- endothelial activation
- permeability
- leukocyte adhesion
How are endothelial cells structured? (3)
Have a large surface area: endothelium is >1000m2
They’re very flat and around 1-2 um thick and 10-20um in diameter
Form a monolayer of endothelial cells which is 1 cell thick (contact inhibition)
What are 4 things that an activated endothelium leads to?
Thrombosis
Permeability
Senescence
Leukocyte recruitment
What are risk factors and stimuli for endothelial cell dysfunction? (10)
Hypercholesterolaemia Diabetes mellitus/ metabolic syndrome Hypertension Sex hormone imbalance Aging Oxidative stress Proinflammatory cytokines Infectious agents Environmental toxins Hydrodynamic forces
