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BRS 2 > Vascular Endothelium > Flashcards

Vascular Endothelium Flashcards

1
Q

What are the three main layers of the vascular endothelium?

A

Tunica adventitia
Tunica media
Tunia intima

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2
Q

What is found within the tunica adventitia?

A

Vaso vasorum

Nerves

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3
Q

Which types of fibres form the tunica media?

A

Smooth muscle cells and elastic fibres

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4
Q

What is the tunica intima?

A

Endothelium

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5
Q

Which cells support the venule and capillary endothelium?

A

Mural cells (pericytes)

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6
Q

What is the function of pericyte?

A

Maintains homeostatic and haemostatic function

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7
Q

What are the main functions of the microvascular endothelium? (6)

A
  • Release angiocrine factors
  • Regulate permeability of vessels
  • Regulate immune response
  • Angiogenesis
  • Vascular tone
  • Haemostasis and thrombosis
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8
Q

Which factor is secreted by the endothelium and mediates platelet adhesion?

A

Von Willebrand Factor

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9
Q

What is endothelial heterogeneity?

A

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

The endothelial phenotype is dependent on location

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10
Q

What are the three types of endothelium?

A

Fenestrated continuous endothelium

Non-fenestrated continuous endothelium

Discontinuous

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11
Q

Where are fenestrated continuous endothelium found?

A

Kidney glomerulus, and gastrointestinal tract to facilitate filtration and absorption

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12
Q

Where are the non-fenestrated continuous endothelium found?

A

In muscle and blood brain barrier

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13
Q

What type of endothelium forms the blood brain barrier?

A

Non-fenestrated

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14
Q

What type of endothelium is found within the liver?

A

Discontinuous

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15
Q

What type of layer is formed by the endothelium?

A

Monolayer

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16
Q

Which types of proteins are involved in cell adhesion and the formation of the monolayer?

A

E-cadherins

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17
Q

Which process arrests cell growth when cells come in contact with each other?

A

Contact inhibition

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18
Q

Describe the proliferation rate in endothelial cells

A

Low proliferation rate unless angiogenesis is induced

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19
Q

What is the resting equilibrium in endothelial cells?

A

A balance between anti-inflammatory, anti-thrombotic and anti-proliferative factors with

pro-inflammatory, pro-thrombotic and pro-angiogenic factors

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20
Q

Which factors activate the endothelium?

A 
OxLDL, 
High glucose, 
High blood pressure, 
Inflammation, 
Mechanical stress, 
Viruses, 
Smoking
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21
Q

What are the responses of the activated endothelium?

A

Thrombosis
Senescence
Permeability
Leukocyte recruitment

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22
Q

What are the matrix products involved in angiogenesis?

A 
Fibronectin 
Laminin
Collagen
Proteoglycans
Proteases
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23
Q

What are the growth factors concerned with angiogenesis?

A

Insulin-like growth factor
Transforming growth factor
Colony stimulating factor

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24
Q

Which adhesion molecules exist on the endothelium and promote neutrophil migration?

A

ICAM and VCAM

Selectins - P-selectin

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25
Q

Which inflammatory mediators are secreted by the endothelium?

A

IL-1, 6, 8
Leukotrienes
MHC-II

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26
Q

What are the four main functions of the endothelium?

A

Angiogenesis
Inflammation
Vascular tone and permeability
Thrombosis and haemostasis

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27
Q

Which type of factor is endothelin?

A

Vasoconstricting factor

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28
Q

Which type of factor is thromboxane A2?

A

Vasoconstricting factor

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29
Q

What are the vasoconstricting factors released by the endothelium?

A 
Angiotensin-Converting Enzymes (ACE)
Thromboxane A2
Leukotrienes
Free radicals
Endothelin
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30
Q

What are the two vasodilator factors released by the endothelium?

A

Nitric oxide

Prostacyclin

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31
Q

What are the procoagulant factors that are released by the endothelium?

A
  • Von Willebrand factor
  • Thromboxane A2
  • Thromboplastin
  • Factor V
  • Platelet activating factor
  • Plasminogen activator inhibitor
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32
Q

What are the anti-thrombotic factors released by the endothelium?

A

• Prostacyclin,

thrombomodulin, antithrombin, PA heparin.

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33
Q

What is the first step of the pathogenesis of atherosclerosis?

A

Increased endothelial permeability to lipoproteins and plasma constituents mediated by nitric oxide, prostacyclin, platelet derived growth factor and endothelin.

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34
Q

Which molecules are upregulated by leukocytes that promote adhesion to the endothelium?

A

Leukocyte adhesion molecules:
L-selectin
Intregrins and platelet endothelial cell adhesion molecule

35
Q

Which molecules are upregulated by endothelial cells that promote leukocyte adhesion

A

Endothelial adhesion molecules E and P-selectin

36
Q

Which molecules promote the migration of leukocytes into the artery wall?

A 
Mediated by low-density lipoprotein
MCP-I
IL-8
Osteopontin 
M-CSF
37
Q

Which molecules are released by macrophages which oxidise LDLs?

A

Free oxygen radicals

38
Q

The phagocytosis of OxLDLs by macrophages forms what type of cell?

A

Foam cell

39
Q

Fatty streak accumulation within the tunica media induces a fibrotic repair process forming what?

A

A fibrous cap

40
Q

What is ultimately formed due to foam cell formation within the tunica media?

A

A necrotic core formed from leukocytes , lipids and debris

41
Q

Which factors promote macrophage migration into the sub-endothelium?

A

MCP-I, MCSF and oxidised low density lipoprotein

42
Q

What does the necrotic core represent?

A

Represents the results of apoptosis and necrosis, increased proteolytic activity and lipid accumulation

43
Q

What factors contribute towards endothelial cell dysfunction?

A

Hyperchoelsterolemia

Diabetes mellitus/metabolic syndrome

Hypertension

sex-hormonal imbalance

Ageing

Oxidative stress

Pro-inflammatory cytokines

infectious agents

Environmental toxins

haemodynamic forces

44
Q

What are the four stages of the pathogenesis of atherosclerosis?

A
  1. Leukocyte recruitment
  2. Permeability
  3. Shear stress
  4. Angiogenesis
45
Q

Which chemokine promotes neutrophil migration?

A

IL-8

46
Q

Which inflammatory cell releases IL-8?

A

Macrophage

47
Q

What are the functions of IL-8?

A

Chemoattractant of neutrophils

Upregulates endothelial adhesion molecules (selectins)

48
Q

What are the first stages of neutrophil migration?

A

Rolling and adhesion occurs as neutrophils establish reversible binding between selectins on the endothelial surface and carbohydrate ligands.

49
Q

Which tight adhesive molecules are found on neutrophils and interact with the endothelium?

A

MAC-I

LFA-I

50
Q

Which tight adhesive molecules are found on the endothelium to interact with migrating neutrophils?

A

ICAM-I and 2 ligands

51
Q

What is diapedesis?

A

The movement of neutrophils from the circulation into the tissues

52
Q

Which molecules foster transcellular interactions for neutrophils?

A

PECAM and JAM interactions

53
Q

Where does the majority of leukocyte transmigration occur?

A

Post-capillary venules

54
Q

What surrounds the capillary?

A

Basement membrane and pericapillary cells (pericytes)

55
Q

Which CD marker is produced by endothelial cells and contribute to diapedesis?

A

CD99

56
Q

What is the function of CD99?

A

Upregulates laminin binding integrin

57
Q

How do neutrophils transmigrate into tissues?

A
  • Infiltrating neutrophils disrupt the interaction of junctional adhesion molecules (JAM) and vascular endothelial cadherins.
  • Neutrophils display motility involving membrane protrusions and the rearrangement of the cytoskeleton of pseudopodia - Mediated by PECAM interactions on both cells.
58
Q

Where do leukocytes transmigrate into?

A

Tunica intima and subendothelial space

59
Q

What is found in the subendothelial space?

A

Extracellular matrix of proteoglycans and lipids

60
Q

What is the effect of increasing endothelial permeability and atherosclerosis?

A

Lipoproteins pass through the fenestrations into the subendothelial space.

Macrophages transmigrate into the subendothelial space, detecting LDLs via scavenger receptors

61
Q

Which type of macrophage receptors detect lipoproteins?

A

Scavenger receptors

62
Q

What forms foam cells?

A

Oxidised lipoproteins within macrophages

63
Q

Which areas potentiate atheroma formation?

A

Curvatures and bifurcations (Ascending aorta and the aortic bifurcation of the abdominal aorta) results in non-uniform haemodynamic forces, potentiating the probability of atheroma formation

64
Q

How do plaques affect shear stress?

A

Narrows the arterial lumen disrupting the laminar flow, thus blood flows in a turbulent manner reducing shear stress that is exerted onto the vascular endothelial cells -disturbing the homeostatic balance that ultimately leads to thrombosis and inflammation

65
Q

What is laminar flow?

A

Blood flows in discrete current lines with minimal interference with each other

66
Q

What are the three characteristics of laminar flow?

A
  • Velocity is constant at any one point, flowing in layers.
  • Blood flows fastest at the centre of flow.
  • Wall shear stress exerted on the endothelium is high and directional.
67
Q

When is shear stress high on the endothelium?

A

During laminar flow

68
Q

What happens to shear stress during turbulent flow?

A

In branches and curvatures, blood flow is distributed with nonuniform and irregular distribution of low wall shear stress.

69
Q

What does laminar flow promote?

A

factors
• Endothelial survival
• Inhibition of Smooth Muscle Cell proliferation
• Nitric oxide (NO) production (Vasodilator)

70
Q

What happens to nitric oxide production in turbulent flow?

A

Decreases NO production

71
Q

What happens to smooth muscles in turbulent flow?

A

Smooth muscle cell proliferation

72
Q

What type of environment is maintained by laminar flow?

A

High shear stress exerted onto the endothelium by laminar flows maintains an antithrombotic and anti-inflammatory environment.

73
Q

What happens during turbulent flow?

A
  • Thrombosis, inflammation (leukocyte adhesion)
  • Endothelial apoptosis
  • Smooth Muscle Cell proliferation
  • Loss of Nitric oxide (NO) production
74
Q

What is the function of nitric oxide released by endothelial cells on lipoproteins?

A

NO reduces the oxidation of LDL cholesterol (major component of plaque)

75
Q

What effect is exerted by NO on platelets?

A

Anti-thrombotic, reduces platelet activation.

76
Q

What effect does NO have on the vessels?

A

Dilation of blood vessels

77
Q

What effect does NO have on superoxides?

A

NO reduces the release of superoxide radicals from macrophages and neutrophils

78
Q

What are the 6 main functions of nitric oxide?

A
  • Reduces platelet activation  Anti-thrombotic
  • Reduces release of superoxide radicals from macrophages and neutrophils.
  • Dilates blood vessels
  • Reduces proliferation of smooth muscle cell within the tunica media
  • Inhibits monocyte adhesion
79
Q

Which factor stimulates angiogenesis in hypoxic conditions?

A

Hypoxia inducible factor stimualtes epo production and potentiates activity of angiogenesis.

80
Q

What are the benefits of angiogenesis?

A

Embryonic development, menstural cycle and wound healing

81
Q

What is the janus paradox?

A

Angiogenesis within the vaso vasorum of the adventitia promotes plaque formation

Revascularisation uses the principle of angiogenesis for therapeutic treatment of post-ischaemic coronary arteries.

82
Q

What is the therapeutic treatment of post-ischaemic coronary arteries?

A

Revascularisation

83
Q

What is a marker of endothelial injury?

A

Circulating endothelial cells

BRS 2 (62 decks)

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