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BRS CARDIO & RESPIRATORY > 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 (7)?

A

IMO VGSH:

  • Inflammation
  • Mechanical stress
  • Ox LDL
  • Viruses
  • Glucose (high)
  • Smoking
  • High blood pressure
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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

Larger tumours require new vessels - tumour cells secrete angiogenic factors that stimulate neovessel formation by endothelial cells in adjacent vessels

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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
Q

In response to injury, what is the pathogenesis of atherosclerosis?

A

1 - Endothelial Dysfunction in Atherosclerosis
= Endothelial permeability ↑
= Leukocyte migration ↑ into the subendothelial space
= Leukocyte adhesion = ↑

2 - Fatty Streak Formation in Atherosclerosis
= fatty-Streak Formation

  1. Formation of an advanced lesion
    = Macrophage accumulation
    = Formation of necrotic core
    = Angiogenesis
26
Q

Recruitment of blood leukocytes into tissues normally takes place during inflammation, where do leukocytes adhere to?

A

Adhere to endothelium of post-capillary venules and transmigrate into tissues

27
Q

In atherosclerosis, where do leukocytes adhere to and what happens after it does this?

A

Activated endothelium of large arteries

Gets stuck in the subendothelial space

28
Q

What is a post-capillary venules?

A

Structure similar to capillaries but more pericytes

29
Q

What happens to monocytes when they migrate to the sub-endothelial space?

A

Differentiate into macrophages and become foam cells

30
Q

What is the endothelium important in regulating?

A

The flux of fluids and molecules from blood to tissues and vice verca

31
Q

What is the consequence of increased vascular permeability?

A

Results in leakage of plasma proteins through the junctions into the sub-endothelial space

32
Q

How does the increased permeability of the endothelium lead to atherosclerosis?

A

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
Q

Where do atherosclerotic plaques preferentially occur?

A

At bifurcations and curvatures of the vascular tree

34
Q

Why do atherosclerotic plaque prefer to occur at bifurcations of blood vessels?

A

The flow patterns and haemodynamics forces are not uniform in the vascular system

35
Q

What is the wall shear stress?

A

Force per unit area exerted by the wall on the fluid in a direction on the local tangent plane

36
Q

In straight parts of the arterial tree what is the wall shear stress described as?

A

high and directional

37
Q

In branches and curvatures, how is blood flow disturbed and what is the resultant effect on wall shear stress?

A

Blood flow is disturbed with non-uniform and irregular distribution of low wall shear stress

38
Q

What four things does laminar blood flow promote?

A

Anti-thrombotic, anti-inflammatory factors
Endothelial survival
Inhibition of Smooth muscle cell (SMC) proliferation
Nitric Oxide (NO) production

39
Q

What does disturbed blood flow promote?

A

Thrombosis

Inflammation (leukocyte adhesion)

Loss of Nitric Oxide production

Endothelial apoptosis

SMC proliferation

40
Q

What are 6 functions of Nitric Oxide that make it essential for the health of the cardiovascular system?

A
  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
Q

What does angiogenesis promote?

A

Plaque growth

Therapuetic angiogenesis prevents damage post-ischemia

42
Q

Is coagulopathy associated with high or low levels of D-Dimers (protein fragment made when a blood clot dissolves in your body) and Fibrinogen?

A

high

43
Q

In severe Covid-19, what could be used as a marker for endothelial injury?

A

Levels of circulating endothelial cells

High D-Dimer levels would be a marker for disease progression

-

44
Q

How are endothelial cells involved in the propagation of COVID-19 infection?

A

SARS-CoV2 Infection = Cytokine storm = endothelial activation = procoagulant switch

45
Q

How would you decrease the increased circulating endothelial cells in COVID-19 patients due to endothelial damage?

A

Give anticoagulants

46
Q

What does a higher than normal D-Dimer level mean?

A

That you have significant blood coagulation

47
Q

High levels of troponin?

A

An issue with the heart as it releases troponin into the blood following an injury such as a myocardial infarction

48
Q

What is the main 2 mechanisms by which COVID can cause activation and damage to the endothelium?

A

Cytokine storm secondary to SARS-CoV2 infection causes endothelial damage

SARS-CoV2 enters endothelial cells and causes direct damage

49
Q

Is ACE2 expressed on epithelial or endothelial cells?

A

Epithelial

50
Q

Does SARS-CoV2 replicate in endothelial cells?

A

no

51
Q

What are the factors which the microvascular endothelial cells produce?

A

Angiocrine factors

52
Q

What are angiocrine factors?

A

Angiocrine factors are factors which can promote the tissue repair of specific tissues - vital for the maintenance of tissue homeostasis and regeneration

53
Q

What influences the phenotype of the endothelial cells?

A

The tissue-specific microenvironment influences the phenotype of the endothelial cels

54
Q

What is the most abundant cells type in the myocardium?

A

Endothelial cells

55
Q

What is single-cell RNA sequencing?

A

helps to examine the sequence information from individual cells and look at their expression profile

56
Q

What are some pathological causes of angiogenesis?

A

Cancer
Chronic Inflammation
Atherosclerosis
Retinopathies
Ischaemic Disease

57
Q

What does the tunica adventitia consist of

A

Vasa vasorum and nerves

58
Q

What does the tunica media consist of?

A

External elastic membrane and smooth muscle

59
Q

What does the tunica intima consist of?

A

Internal elastic membrane
Lamina propria
Basement membrane
Endothelium

60
Q

Describe the structure of capillaries?

A

Formed by only endothelium, supported by mural cells (pericytes) and a basement membrane

61
Q

Where do the majority of endothelial cells reside?

A

Within the microvasculature

62
Q

What are the different types of endothelial cells?

A

Continuous (fenestrated and non-fenestrated) and Non continuous

BRS CARDIO & RESPIRATORY (26 decks)

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