Vascular Endothelium Flashcards
1
Q
What are the 3 layers of blood vessels (from outermost to innermost)?
A
- tunica adventitia
- tunica media
- tunica intima
2
Q
What makes up the tunica adventitia?
A
- vasa vasorum
- nerves
3
Q
What makes up the tunica media?
A
- external elastic membrane
- smooth muscle
4
Q
What makes up the tunica intima?
A
- internal elastic membrane
- lamina propria
- endothelium
5
Q
What is the lamina propria?
A
- smooth muscle
- connective tissue
6
Q
What are capillaries and venules comprised of?
A
- endothelium
- pericytes (mural cells)
- basement membrane
7
Q
What happens at capillaries?
A
exchange of nutrients and oxygen between blood and tissues
8
Q
What does the microvascular endothelium do?
A
- source of angiocrine factors
- promote tissue homeostasis and organ regeneration
9
Q
What is the impact of a dysfunctional endothelium?
A
- contributes to disease
- ischemia
- chronic inflammatory diseases
- cancer
- diabetes
- atherosclerosis
10
Q
Do endothelium cells vary?
A
- yes, they have organotypic properties and expression profiles
- have structural, functional and molecular differences
11
Q
What are the properties of endothelial cells in the muscle, lung, skin and blood brain barrier?
A
continuous non-fenestrated
12
Q
What are the properties of endothelial cells in the kidney glomerulus, GI tract?
A
continuous fenestrated
13
Q
What are the properties of endothelial cells in the liver and marrow?
A
discontinuous
14
Q
What are the properties of endothelial cells?
A
- very flat
- about 1-2 micrometers thick
- about 10-20 micrometers in diameter
15
Q
What is contact inhibition?
A
when the junctions of 2 cells join and establishes a junction causing the cells to stop growing
16
Q
What is the lifespan of endothelial cells?
A
- long
- low proliferation rate
(unless angiogenesis is necessary)
17
Q
What are the functions of endotheliun?
A
- vascular tone
- permeability
- angiogenesis
- haemostasis and thrombosis
- inflammation
18
Q
What happens when the endothelium is at rest?
A
promotion of:
- anti-inflammatory
- anti-thrombotic
- anti-proliferative
19
Q
What happens when the endothelium is activated?
A
promotion of:
- pro-inflammatory
- pro-thrombotic
- pro-angiogenic
20
Q
What activates the endothelium?
A
- smoking
- viruses
- mechanical stress
- inflammation
- high BP
- OxLDL
- high glucose
21
Q
What happens when there is long term/chronic activation of the endothelium?
A
- thrombosis
- senescence
- permeability
- leukocyte recruitment
all cause: atherosclerosis
22
Q
What are the characteristics of endothelial dysfunction in atherosclerosis?
A
- endothelial permeability
- leukocyte migration
- endothelial adhesion
- leukocyte adhesion
23
Q
What happens in the fatty-streak formation in atherosclerosis?
A
- smooth muscle migration
- foam cell formation
- t cell activation
- adherence and aggregation of platelets
- adherence and entry of leukocytes
24
Q
What happens in the formation of an advanced, complicated lesion of atherosclerosis?
A
- macrophage accumulation
- formation of a necrotic core
- angiogenesis
- fibrous cap formation
25
What are the triggers of endothelial dysfunction in atherogenesis?
- oxidative stress
- pro-inflammatory cytokines
- infectious agents
- environmental toxins
- haemodynamic forces
26
What are the risk factors of endothelial dysfunction causing atherogenesis?
- hypercholesterolaemia
- DM/metabolic syndrome
- hypertension
- sex hormonal imbalance
- ageing
27
What are the mechanisms that contribute to the development of atherosclerosis?
- leukocyte recruitment
- permeability
- shear stress
- angiogenesis
28
What happens in the leukocyte adhesion cascade?
- capture
- rolling and arrest (activation)
- adhesion
- spreading
- paracellular and transcellular transmigration
29
When and where does leukocyte recruitment normally occur?
during inflammation, leukocytes adhere to the post-capillary venules before entering the tissues
30
What is the structure of a capillary?
- endothelial cells
- basement membrane
- pericapillary cells (pericytes)
31
What is the difference in the structure of a capillary and a post-capillary venule?
venules have more pericytes (pericapillary cells)
32
Where does leukocyte recruitment occur in atherosclerosis?
- adhere to the activated endothelium of of large arteries and are stuck in the sub-endothelial space
- monocytes differentiate into macrophages and then foam cells in the subendothelial space
33
What happens when there is increased permeability of the endothelium?
- leakage of plasma proteins through the junctions into the subendothelial space
- LDL enters the subendotheial space and becomes OxLDL which further activates endothelial cells
- macrophages take up OxLDL and become foam cells
34
What happens to blood flow in the straight parts of the arterial tree?
- laminar blood flow
- high and directional wall shear stress
35
What happens to blood flow in the branches and curvatures of the arterial tree?
- disturbed blood flow
- non-uniform and irregular distribution of low wall shear stress
36
What does laminar blood flow promote?
- anti-thrombotic, anti-inflammatory factors
- endothelial survival
- inhibitions of SMC proliferation
- NO production
37
What does disturbed blood flow promote?
- thrombosis, inflammation (leukocyte adhesion)
- endothelial apoptosis
- SMC proliferation
- loss of NO production
38
What is the role of NO?
key regulator of vascular function
- reduces OxLDL
- vasodilation
- reduces platelet activation
- inhibits monocyte adhesion
- reduces release of superoxide radicals
- reduces SMC proliferation
39
What is angiogenesis?
formation of new blood vessels by sprouting from existing ones
40
What is angiogenesis triggered by?
hypoxia
41
What is angiogenesis essential for?
- embryonic development
- wound healing
- menstrual cycle
42
What is the double role of angiogenesis?
- promotes plaque growth
- theraputic angiogenesis prevents damage post-ischemia
43
What is pathological angiogenesis associated with?
advanced atherosclerotic plaques
44
What is associated with a poor prognosis with a COVID infection?
- increased D-Dimers
- increased fibrinogen
45
Where are the majority of endothelial cells?
capillaries
46
What is thromboinflammation?
loss of the normal anti-thrombotic and anti-inflammatory functions of endothelial cells causes thrombosis with associated inflammation
47
How does covid cause endothelial dysfunction?
- cytokine storm
- endothelial activation
- procoagulant switch
48
What are the 2 possible ways that SARS-CoV2 causes endothelial damage?
- cytokine storm secondary to the infection causes the endothelial damage
- SARS-CoV2 enters the cells and causes direct damage (no evidence)
49
What functions of blood vessels and tissues does the endothelium control?
- vascular tone
- angiogenesis
- haemostasis and thrombosis
- inflammation
- permeability
50
How do endothelial cells regulate thrombosis and haemostasis?
Antithrombotic and procoagulant factors
51
How do endothelial cells regulate angiogenesis?
Growth factors (e.g IGF) and matrix products
52
How do endothelial cells regulate vascular tone and permeability?
Vasconstricting and vasodilating factors
53
How do endothelial cells regulate inflammation?
Inflammatory modulators and adhesion molecules
54
How are the transcriptional signatures of individual cells examined?
- single cell RNAseq
- shown on a seurat cluster graph, each dot is a cell and each cell is grouped according to the similarities in their gene expression
55
What influences the phenotype of endothelial cells?
Tissue-specific microenvironment
56
How are new blood vessels formed?
Sprouting angiogenesis
57
Which pathologies does angiogenesis play a role in?
Cancer
Retinopathies
Atherosclerosis
Chronic inflammatory diseases
Ischemic diseases
Vascular malformations
58
What is an angiogenic switch?
- tumour cells in large tumours secrete angiogenic factors that stimulate new vessel formation by endothelial cells in adjacent vessels
- this facilitates tumour growth and metastasis
59
What is Von Willebrand disease?
- most common hereditary bleeding disorder (1/100)
- caused by dysfunction of Von Willebrand factor
60
How is VWD treated?
VWF or DDAVP
61
What causes severe, intractable bleeding in the GIT in patients eith VWD?
- Vascular malformations in the gut blood vessels
- cannot be treated with VWF replacement
62
What is the role of VWF in haemostasis?
- mediates platelet adhesion to the subendothelium and platelet aggregation
- stabilises circulating coagulation Factor VIII
63
What is the role of VWF in angiogenesis?
- regulates growth factor signalling (VEGFR2:Ang-2)
64
Where do atheroscleoritc plaques usually occur and why?
- at bifurcations and curvaturesof the vascular tree
- flow patterns and haemodynamic forces are not uniform in the vascular system
