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CARDIO & RESPIRATORY - BRS > 1b Vascular Endothelium > Flashcards

1b Vascular Endothelium Flashcards

1
Q

What are blood vessels lined by?

A

Endothelial cells

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2
Q

What are the three layers of blood vessels, except capillaries and venules?

A

Tunica Adventitia
Tunica Media
Tunica Intima - endothelium

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3
Q

What is contained within the lamina propria?

A

Smooth muscle and connective tissue

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4
Q

What is the site of exchange of nutrients and oxygen between blood and tissues?

A

Capillaries

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5
Q

What 2 features are capillaries and venules supported by?

A

Mural cells (pericytes) - regulate blood vessel diameter

Basement membrane - filter for substances

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6
Q

What properties do endothelial cells have?

A

Organotypic - tissue specific properties with unique gene/protein expression proteins

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7
Q

Why does microvasculature look different in different organs?

A

Endothelial cells are heterogenic

Endothelial cells and microvasculature have organotypic (tissue-specific) properties and expression profiles

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8
Q

What is the surface area and weight of the endothelium?’

A

Surface area > 1000m^2

Weight > 100g

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9
Q

What is contact inhibition?

A

Endothelial cells forming cell-cell junctions signal to one another when they make contact to inhibit each other’s further growth

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10
Q

What is the proliferation rate of endothelial cells?

A

Low proliferation rates, unless new vessels are required = angiogenesis

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11
Q

What are the 6 main functions of blood vessels and tissues that are controlled by endothelium?

A

Permeability
Angiogenesis
Vascular Tone
Inflammation
Tissue homeostasis and regeneration
Haemostasis and Thrombosis

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12
Q

At resting state, what does the endothelium induce with respect to inflammation, thrombosis and proliferation?

A

The endothelium is:

Anti-inflammatory

Anti-thrombotic

Anti-proliferative

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13
Q

When activated, how does the endothelium change to suit a pro-inflammatory environment?

A

The endothelium is:

Pro-inflammatory

Pro-thrombotic

Pro-angiogenic

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14
Q

What different environmental / physiological factors can lead to an activated endothelium?

A

Inflammation

Mechanical stress

Ox LDL

High blood pressure

Smoking

Viruses

High glucose

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15
Q

What is angiogenesis?

A

The formation of new vessels by sprouting from existing vessels

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16
Q

What is the main trigger for agiogenesis?

A

Hypoxia

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17
Q

What three physiological events is angiogenesis needed for?

A

Development
Menstrual Cycle
Wound Healing

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18
Q

What 4 things can an activated endothelium lead to, as implicated in the pathophysiology of atherosclerosis?

A

1) Thrombosis

2) Leukocyte recruitment

3) Senescence - cell stops dividing but does not die

4) Permeability

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19
Q

How do tumours stimulate angiogenesis?

A

Secretes angiogenic factors that stimulate migration, proliferation and neovessel formation by endothelial cells in adjacent established vessels

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20
Q

What is the angiogenic switch?

A

a discrete step in tumour development that can occur at different stages in the tumour progression pathway, depending on the nature of the tumour and its microenvironment

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21
Q

Describe the shape of tumour blood vessels?

A

Irregularly shapes, dilated, tortuous

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22
Q

How are tumour blood vessels organised?

A

Not into definitive venules, arterioles and capillaries

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23
Q

What are two characteristics of tumour blood vessels?

A

leaky and heamorrhagic = due to overproduction of VEGF

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24
Q

What is thromboinflammation?

A

Loss of anti-thrombic and anti-inflammation functions of endothelial cells causing thrombosis with associated inflammation

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25
In response to injury, what is the pathogenesis of atherosclerosis??
1 - Endothelial Dysfunction in Atherosclerosis = Endothelial permeability ↑ = Leukocyte migration ↑ into the subendothelial space = Leukocyte adhesion = ↑ 2 - Fatty Streak Formation in Atherosclerosis = fatty-Streak Formation 3. Formation of an advanced lesion = Macrohpgae accumulation = Formation of necrotic core = Angiogenesis
26
Recruitment of blood leukocytes into tissues normally takes place during inflammation, where do leukocytes adhere to?
Adhere to endothelium of post-capillary venules and transmigrate into tissues
27
In atherosclerosis, where do leukocytes adhere to and what happens after it does this?
Activated endothelium of large arteries Gets stuck in the subendothelial space
28
What is a post-capillary venules?
Structure similar to capillaries but more pericytes
29
What happens to monocytes when they migrate to the sub-endothelial space?
Differentiate into macrophages and become foam cells
30
What is the endothelium important in regulating?
The flux of fluids and molecules from blood to tissues and vice verca
31
What is the consequence of increased vascular permeability?
Results in leakage of plasma proteins through the junctions into the sub-endothelial space
32
How does the increased permeability of the endothelium lead to atherosclerosis?
Lipoproteins enter subendothelium through weaknesses in the endothelium which then bind to proteoglycans and the lipoproteins are oxidated in the environment of the subendothelium Macrophages come and agglutinate the proteoglycan-lipoprotein complexes which leads it to become a foam cell
33
Where do atherosclerotic plaques preferentially occur?
At bifurcations and curvatures of the vascular tree
34
Why do atherosclerotic plaque prefer to occur at bifurcations of blood vessels?
The flow patterns and haemodynamics forces are not uniform in the vascular system
35
What is the wall shear stress?
Force per unit area exerted by the wall on the fluid in a direction on the local tangent plane
36
In straight parts of the arterial tree what is the wall shear stress described as?
high and directional
37
In branches and curvatures, how is blood flow disturbed and what is the resultant effect on wall shear stress?
Blood flow is disturbed with non-uniform and irregular distribution of low wall shear stress
38
What four things does laminar blood flow promote?
Anti-thrombotic, anti-inflammatory factors Endothelial survival Inhibition of SMC proliferation Nitric Oxide (NO) production
39
What does disturbed blood flow promote?
Thrombosis Inflammation (leukocyte adhesion) Loss of Nitric Oxide production Endothelial apoptosis SMC proliferation
40
What are 6 functions of Nitric Oxide that make it essential for the health of the cardiovascular system?
1. Vasodilation 2. reduce platelet activation 3. Inhibits monocyte adhesion 4. Inhibits proliferation of SMC in the vessel wall 5. Reduces release of superoxide radicals 6. Reduces oxidation of LDL cholesterol (major constituent of plaque)
41
What does angiogenesis promote?
Plaque growth Therapuetic angiogenesis prevents damage post-ischemia
42
Is coagulopathy associated with high or low levels of D-Dimers and Fibrinogen?
high
43
In severe Covid-19, what could be used as a marker for endothelial injury?
Levels of **circulating endothelial cells** **High D-Dimer** levels would be a marker for disease progression -
44
How are endothelial cells involved in the propagation of COVID-19 infection?
SARS-CoV2 Infection = Cytokine storm = endothelial activation = procoagulant switch
45
How would you decrease the increased circulating endothelial cells in COVID-19 patients due to endothelial damage?
Give anticoagulants
46
What does a higher than normal D-Dimer level mean?
That you have significant blood coagulation
47
High levels of troponin?
An issue with the heart as it releases troponin into the blood following an injury such as a myocardial infarction
48
What is the main 2 mechanisms by which COVID can cause activation and damage to the endothelium?
**Cytokine storm** secondary to SARS-CoV2 infection causes endothelial damage SARS-CoV2 enters endothelial cells and causes **direct damage**
49
Is ACE2 expressed on epithelial or endothelial cells?
Epithelial
50
Does SARS-CoV2 replicate in endothelial cells?
no
51
What are the factors which the microvascular endothelial cells produce?
Angiocrine factors
52
What are angiocrine factors?
Angiocrine factors are factors which can promote the tissue repair of specific tissues - vital for the maintenance of tissue homeostasis and regeneration
53
What influences the phenotype of the endothelial cells?
The tissue-specific microenvironment influences the phenotype of the endothelial cels
54
What influences the phenotype of the endothelial cells?
The tissue-specific microenvironment influences the phenotype of the endothelial cells
55
What is the most abundant cells type in the myocardium?
Endothelial cells
56
What is single-cell RNA sequencing?
helps to examine the sequence information from individual cells and look at their expression profile
57
What are some pathological causes of angiogenesis?
Cancer Chronic Inflammation Atherosclerosis Retinopathies Ischaemic Disease
58
What does the tunica adventitia consist of
Vasa vasorum and nerves
59
What does the tunica media consist of?
External elastic membrane and smooth muscle
60
What does the tunica intima consist of?
Internal elastic membrane Lamina propria Basement membrane Endothelium
61
Describe the structure of capillaries?
Formed by only endothelium, supported by mural cells (pericytes) and a basement membrane
62
Where do the majority of endothelial cells reside?
Within the microvasculature
63
What are the different types of endothelial cells?
Continuous (fenestrated and non-fenestrated) and Non continuous

CARDIO & RESPIRATORY - BRS (28 decks)

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