vascular endothelium

Question 1

what are the 3 layers of blood vessels

Answer 1

endothelium- tunica intima

smooth muscle cells- tunica media

vasa vasorum/nerves- tunica adventitia

Question 2

purpose of endothelium

Answer 2

barrier separating blood from tissue

Question 3

endothelium controls multiple functions of blood vessels and tissues. Give 6 examples

Answer 3

• tissue homeostasis and regeneration
  -permeability
  -inflammation
  -angiogenesis
  -vascular tone
  -haemostasis and thrombosis

Question 4

not all endothelial cells in body are the same: structural, function and molecular differences, what is the name for the differences

Answer 4

-organotypic (tissue-specific) properties
-gene/protein expression profiles

Question 5

what can be used to examine transcriptional signature of individual cells

What is it called when each dot is a cell. Cells are grouped with similar gene expression)

Answer 5

single cell RNAseq

(Results- Seurat clustering: each dot is a cell. Cells are grouped with similar gene expression)

Question 6

what is the Human Cell Atlas

Answer 6

mapping all cell types in human body at single cell level

Question 7

• tissue homeostasis and regeneration being one of endothelial cell function- elaborate : what it can produce,

Answer 7

produce Angiocrine factors- maintenance of tissue homeostasis and regeneration.

Question 8

most abundant cell type in heart and what it can do in the heart

Answer 8

1. endothelial cells
2. myocytes
3. stromal cells

crosstalk with cardiomyocyte

Question 9

angiogenesis steps

Answer 9

1. hypoxia- angiogenic factor production+ release

2.endothelial cell receptors bind, activate and proliferate

3. ECM remodelling, tube formation and vascular stabilisation

Question 10

angiogenesis - physiology vs pathology

Answer 10

physiology: wound healing/menstrual cycle

pathology: cancer/atherosclerosis

Question 11

cancer growth and angiogenic switch - explain steps

Answer 11

1. small tumour receive oxygen and nutrients via diffusion from host vasculature
2. larger tumours need new vessels. Tumour secrete angiogenic factors- new vessel form by endothelial cells in adjacent vessels– angiogenic switch
3. tumour vasculature facilitates growth and metastasis.
4. anti-angiogenic drugs + chemo

Question 13

what is the most common hereditary bleeding disorder.
Main characteristics?
what therapy for mild form?
what is severe bleeding from GI track is due to

Answer 13

VWF decrease/dysfunction.
-mucosal bleeding
-replacement therapy (VWF)
-vascular malformation

Question 14

2 roles of VWF

Answer 14

Haemostasis
-platelet adhesion to subendothelial and platelet aggregation.
-stabilise F8

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

Question 15

steps of pathogenesis of atherosclerosis- response to injury model

Answer 15

1. endothelial dysfunction in atherosclerosis
2. fatty-streak formation- LDL enter vessel wall and taken up by macrophages
3. form advanced, complicated lesions- narrowing artery

Question 16

difference between capillary and post-capillary venules

Answer 16

capillary- endothelial cells surrounded by basement membrane and pericapillary cells (pericytes)

post-capillary venules- similar structure to capillaries but MORE PERICYTES

Question 17

endothelial dysfunction in pathogenesis of atherosclerosis- 4 mechanism

Answer 17

-leukocyte recruitment
-permeability
-shear stress
-angiogenesis

Question 18

how does recruitment of blood leukocyte normally take place+ where

Answer 18

during inflammation- leukocyte adhere to endothelium of post-capillary venules and transmigrate into tissue

Question 19

leukocyte recruitment in atherosclerosis

Answer 19

-leukocyte adhere to activated endothelium of large arteries and stuck in subendothelial space
-monocyte migrate into subendothelial space->differentiate into macrophages->become foam cells after taking up oxidated LDL

Question 20

vascular permeability and lipoprotein trapping

Answer 20

-endothelium regulates permeability ->flux of fluid and molecules between blood and tissue
-endothelial activation- increase permeability and leakage of plasma proteins into subendothelial space

-LDL enter subendothelial space and gets oxidised–> OxLDL– further promotes endothelial activation

Question 21

why does atherosclerosis occur at branch points (bifurcations and curvatures of vascular trees)
(compare this to straight parts)

Answer 21

bifurcations:
blood flow=disturbed+ low wall shear stress

straight parts–>
-blood flow=laminar. Shear wall stress is high and directional.

Question 22

positive effects of laminar blood flow on vascular endothelium///vs disturbed blood flow

Answer 22

laminar–>
produce NO/
anti-inflammatory factors/
endothelial survival/
inhibit SMC proliferation

disturbed–>
loss of produce NO/
inflammatory/
endothelial apoptosis/
SMC proliferation

Question 23

effect of NO on cardiovascular system

Answer 23

dilate blood vessel,
reduce platelet activation,
reduce LDL oxidation,
inhibit monocyte adhesion

Question 24

what is janus paradox

Answer 24

-angiogenesis promotes plaque growth

-therapeutic angiogenesis prevent damage post-ischemia