vascular endothelium

Question 1

basic structure of blood vessel → layers?

Answer 1

tunica adventitia with vasa vasorum, nerves

tunica media with smooth muscle cells

tunica intima with endothelium

Question 2

which vessels are the exception to this structure?

Answer 2

capillaries and venules

Question 3

what are capillaries and venules made from

Answer 3

endothelium supported by mural cells (pericytes) and basement membrane
nearly all cells are in contact with microvascular endothelial cells

Question 4

what kind of layer do these form? (endothelial cells lining the vascular system)

Answer 4

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

Question 5

lifespan of endothelial cells?

Answer 5

long, low proliferation rate unless new vessels are needed

new vessels = angiogenesis

Question 6

what do the endothelial cells control?

Answer 6

vascular tone, angiogenesis, haemostasis and thrombosis, inflammation, permeability, tissue homeostasis and regen

Question 7

are the endothelial layers the same throughout the body?

Answer 7

no as there are structural functional and molecular differences
endothelial cells and microvasculature have organotypic (tissue specific) properties and gene/protein expression profiles

Question 8

how do endothelial cells maintain tissue homeostasis and regeneration?

Answer 8

producing angiocrine factors

Question 9

how does this link to each specific tissue?

Answer 9

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

Question 10

when is angiogenesis usually required?

Answer 10

menstrual cycle, wound healing, development

Question 11

pathological causes of angiogenesis?

Answer 11

cancer, atherosclerosis, retinopathies, chronic inflammatory disease, ischemic disease, vascular malformations etc

Question 12

what is the angiogenic switch?

Answer 12

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

Question 13

main type of bleeding in von willebrand disease?

Answer 13

mucosal

Question 14

when is replacement of deficient/dysfunctional clotting factors insufficient?

Answer 14

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

Question 15

functions of VWF?

Answer 15

platelet adhesion to endothelium, stabilises factor VIII

controls angiogenesis and blood vessel integrity by regulating growth factor signalling (VEGFR2)

Question 16

what characteristics of an activated endothelium can lead to atherosclerosis?

Answer 16

thrombosis, senescence, leukocyte recruitment, increased permeability

Question 17

where do leukocytes migrate from blood into tissues?

Answer 17

mostly in post capillary venules and then transmigrate into tissues
this takes place during inflammation

Question 18

how does leukocyte migration occur

Answer 18

cytokine and chemokine signal → leukocyte undergoes capture, rolling, adhesion and paracellular/transcellular migration

Question 19

how does this contribute to atherosclerosis pathophysiology?

Answer 19

leukocytes adhere to activated endothelium of large arteries → stuck into subendothelial space

monocytes in subendothelial space differentiate → macrophages → foam cells

Question 20

how does vascular permeability contribute?

Answer 20

activated endothelium = more leaky

LDLs allowed to enter subendothelial space → oxidised and promote endothelial activation etc

Question 21

why does atherosclerosis occur at branch points?

Answer 21

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

Question 22

whats the consequence of disturbed flow

Answer 22

loss of nitric oxide NO production

ordinarly it reduces LDL cholesterol oxidation

vasodilation

reduces platelet activation

inhibits smooth muscle proliferation

inhibits monocyte adhesion

reduces superoxide radical release

Question 23

how does angiogenesis relate to atherosclerosis?

Answer 23

angiogenesis contributes to plaque formation

therapeutic angiogenesis can prevent damage after ischaemia

Question 24

in what other illness does endothelial health play an important role?

Answer 24

SARS-CoV-2

Question 25

how to measure endothelial cell heterogenity

Answer 25

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

Question 26

what drugs are used for solid tumours

Answer 26

anti-angiogenic drugs with chemotherapy

Question 27

response to injury model

Answer 27

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

Question 28

laminar blood flow promotes

Answer 28

anti thrombotic anti inflammatory factors
endothelial survival
inhibition of SMC proliferation
NO production