vascular endothelium Flashcards
basic structure of blood vessel → layers?
tunica adventitia with vasa vasorum, nerves
tunica media with smooth muscle cells
tunica intima with endothelium
which vessels are the exception to this structure?
capillaries and venules
what are capillaries and venules made from
endothelium supported by mural cells (pericytes) and basement membrane
nearly all cells are in contact with microvascular endothelial cells
what kind of layer do these form? (endothelial cells lining the vascular system)
acts as a barrier separating blood from tissues
cells are very flat about 1-2 micrometres thick and 10-20 micrometre diameter
thin monolayer one cell deep for contact inhibition
Large SA>1000m2 weight >100g
lifespan of endothelial cells?
long, low proliferation rate unless new vessels are needed
new vessels = angiogenesis
what do the endothelial cells control?
vascular tone, angiogenesis, haemostasis and thrombosis, inflammation, permeability, tissue homeostasis and regen
are the endothelial layers the same throughout the body?
no as there are structural functional and molecular differences
endothelial cells and microvasculature have organotypic (tissue specific) properties and gene/protein expression profiles
how do endothelial cells maintain tissue homeostasis and regeneration?
producing angiocrine factors
how does this link to each specific tissue?
angiocrine profile is tissue specific
tissue specific microenvironment influences phenotype of endothelial cells
endothelial cells are the must abundant cell type in the heart and crosstalk with cardiomyocytes
when is angiogenesis usually required?
menstrual cycle, wound healing, development
pathological causes of angiogenesis?
cancer, atherosclerosis, retinopathies, chronic inflammatory disease, ischemic disease, vascular malformations etc
what is the angiogenic switch?
tumour grows large enough to require new vessels → starts secreting angiogenic factors stimulating new vessel formation in adjacent endothelial cells (angiogenic switch)-> tumour vasculature facilitates growth and metastasis
main type of bleeding in von willebrand disease?
mucosal
when is replacement of deficient/dysfunctional clotting factors insufficient?
some patients = GI tract bleeding due to vascular malformations in the gut blood vessels
replacement therapy eg VWF and DDAVP is given in most mild cases
functions of VWF?
platelet adhesion to endothelium, stabilises factor VIII
controls angiogenesis and blood vessel integrity by regulating growth factor signalling (VEGFR2 ,Ang-2)
what characteristics of an activated endothelium can lead to atherosclerosis?
Leukocyte recruitment,shear stress,, leukocyte recruitment, increased permeability
where do leukocytes migrate from blood into tissues?
mostly in post capillary venules and then transmigrate into tissues
this takes place during inflammation
how does leukocyte migration occur
cytokine and chemokine signal → leukocyte undergoes capture, rolling, adhesion and paracellular/transcellular migration
how does this contribute to atherosclerosis pathophysiology?
leukocytes adhere to activated endothelium of large arteries → stuck into subendothelial space
monocytes in subendothelial space differentiate → macrophages → foam cells
how does vascular permeability contribute?
activated endothelium = more leaky
LDLs allowed to enter subendothelial space → oxidised and promote endothelial activation etc
Endothelial activation causes increased permeability and leakage of plasma proteins into the subendothelial space. LDL Exeter the subendothelal space get oxidized ldl and further promote endothelial activation etc. monocytes migrated into the intima space differentiate into macrophages and take up oxidized LDL making foam cells
why does atherosclerosis occur at branch points?
non-laminar flow creates non-uniform stress with disturbed flow and irregular distribution of low wall shear stress
when flow is laminar wall shear stress is high and directional
whats the consequence of disturbed flow
loss of nitric oxide NO production
ordinarly it reduces LDL cholesterol oxidation
vasodilation
reduces platelet activation
smooth muscle proliferation
inhibits monocyte adhesion
reduces superoxide radical release
how does angiogenesis relate to atherosclerosis?
angiogenesis contributes to plaque formation
therapeutic angiogenesis can prevent damage after ischaemia
in what other illness does endothelial health play an important role?
SARS-CoV-2
Causes cytokine storm which causes endothelial activation thus procoagulant switch
how to measure endothelial cell heterogenity
single cell RNAseq to examine the transcriptional signature of individual cells
cells are dissociated and then isolated. RNA extracted and single cell sequecning occurs where you can see the expression profile after. Seurat clustering where each dot is a cell and cells are grouped according to similarity of gene expression
what drugs are used for solid tumours
anti-angiogenic drugs with chemotherapy
response to injury model
endothelial dysfunction causes adhesion of leukocytes and migration below endothellium to accumulate in sub endothelial space
at the same time endothelial permeability increases so lipids accumulate as well forming a fatty streak which then forms lesions of atherosclerosis
laminar blood flow promotes
anti thrombotic anti inflammatory factors
endothelial survival
inhibition of SMC proliferation
NO production
Disturbed blood flow promotes
Thrombosis
Inflammation (leukocytes adhesion)
SMC proliferation
Loss of NO production
Angiogenesis and cardio disease
Angiogenesis also promotes plaque growth (janus paradox)
NO effects
Reduces oxidation of LDL cholesterol
Reduces release of superoxide radicals
Reduces proliferation of SMC jn vessel wall
Inhibits monocytes adhesion
Reduces platelet activation
Size of capillaries
5-10 micrometers
