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Phase 1b - Cardiovascular & Respiratory Medicine > Vascular Endothelium - In Health and Disease > Flashcards

Vascular Endothelium - In Health and Disease Flashcards

1
Q

What are the 3 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 (2)?

A
  • Vaso vasorum
  • Nerves

Nerves

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3
Q

Which types of fibres form the tunica media (2)?

A
  • Smooth muscle cells
  • 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 surrounds the capillary (2)?

A
  • Basement membrane
  • Pericapillary cells (pericytes)
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7
Q

What is the function of the mural cells (pericytes)?

A
  • Maintains homeostatic & haemostatic function
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8
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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9
Q

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

A

E-cadherins

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10
Q

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

A
  • Contact inhibition
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11
Q

What are the 3 types of endothelium?

A
  • Fenestrated continuous endothelium
  • Non-fenestrated continuous endothelium
  • Discontinuous
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12
Q

Where are fenestrated continuous endothelium found (2)?

A
  • Kidney glomerulus
  • Gastrointestinal tract

To facilitate filtration and absorption

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13
Q

Where are the non-fenestrated continuous endothelium found (4)?

A
  • Muscle
  • Lung
  • Skin
  • Blood brain barrier

To regulate diffusion

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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

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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17
Q

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

A
  • Von Willebrand Factor
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18
Q

What is the resting equilibrium in endothelial cells?

A

A balance between:
* Anti-inflammatory
* Anti-thrombotic
* Anti-proliferative factors
VS
* Pro-inflammatory
* Pro-thrombotic
* Pro-angiogenic factors

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19
Q

Describe the proliferation rate in endothelial cells

A
  • Low proliferation rate unless angiogenesis is induced
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20
Q

What factors contribute towards endothelial cell dysfunction (10 / know 5)?

A
  • Hyperchoelsterolemia
  • Diabetes mellitus / metabolic syndrom
  • Hypertension
  • Sex-hormonal imbalance
  • Ageing
  • Oxidative stress
  • Pro-inflammatory cytokines
  • Infectious agents
  • Environmental toxins
  • Haemodynamic forces
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21
Q

Which factors activate the endothelium (7)?

A
  • OxLDL
  • High glucose
  • High blood pressure
  • Inflammation
  • Mechanical stress
  • Viruses
  • Smoking
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22
Q

What are the responses of the activated endothelium (4)?

A
  • Thrombosis
  • Senescence
  • Permeability
  • Leukocyte recruitment

Senescence: loss of a cell’s power of division and growth

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23
Q

What is a marker of endothelial injury?

A

Circulating endothelial cells

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24
Q

What are the matrix products involved in angiogenesis (5)?

A
  • Fibronectin
  • Laminin
  • Collagen
  • Proteoglycans
  • Proteases
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25
Q

What are the growth factors concerned with angiogenesis (3)?

A
  • Insulin-like growth factor
  • Transforming growth factor
  • Colony stimulating factor
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26
Q

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

A
  • Intercellular adhesion molecule (ICAM)
  • Vascular cell adhesion molecule (VCAM)

Selectins - P-selectin

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27
Q

Which inflammatory mediators are secreted by the endothelium (5)?

A
  • IL-1
  • IL-6
  • IL-8
  • Leukotrienes
  • MHC-II
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28
Q

What are the vasoconstricting factors released by the endothelium (5)?

A
  • Angiotensin-Converting Enzymes (ACE)
  • Thromboxane A2
  • Leukotrienes
  • Free radicals
  • Endothelin
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29
Q

Which type of factor is endothelin?

A
  • Vasoconstricting factor
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30
Q

Which type of factor is thromboxane A2?

A
  • Vasoconstricting factor
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31
Q

What are the 2 vasodilator factors released by the endothelium?

A
  • Nitric oxide
  • Prostacyclin
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32
Q

What are the procoagulant factors that are released by the endothelium (6)?

A
  • Von Willebrand factor
  • Thromboxane A2
  • Thromboplastin
  • Factor V
  • Platelet activating factor
  • Plasminogen activator inhibitor
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33
Q

What are the anti-thrombotic factors released by the endothelium (4)?

A
  • Prostacyclin
  • Thrombomodulin
  • Antithrombin
  • PA heparin
34
Q

What are the four stages of the pathogenesis of atherosclerosis?

A
  1. Leukocyte recruitment
  2. Permeability
  3. Shear stress
  4. Angiogenesis
35
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.
36
Q

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

A
  • A fibrous cap
37
Q

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

A
  • A necrotic core formed from leukocytes , lipids and debris
38
Q

What does the necrotic core represent (3)?

A
  • Represents the results of apoptosis and necrosis, increased proteolytic activity and lipid accumulation
39
Q

Which molecules are upregulated by endothelial cells that promote leukocyte adhesion (2)?

A
  • E-selectin
  • P-selectin
40
Q

Which molecules are upregulated by leukocytes that promote adhesion to the endothelium (3)?

A
  • L-selectin
  • Intregrins
  • Platelet endothelial cell adhesion molecule
41
Q

Which molecules promote the migration of leukocytes into the artery wall (5)?

A
  • Low-density lipoprotein (LDL)
  • MCP-I
  • IL-8
  • Osteopontin
  • M-CSF
42
Q

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

A
  • Foam cell
43
Q

Which molecules are released by macrophages which oxidise LDLs?

A
  • Free oxygen radicals
44
Q

Which factors promote macrophage migration into the sub-endothelium (3)?

A
  • MCP-I
  • MCSF
  • Oxidised low density lipoprotein (OxLDL)
45
Q

What is diapedesis?

A
  • The movement of neutrophils from the circulation into the tissues
46
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
47
Q

Which inflammatory cell releases IL-8?

A

Macrophage

48
Q

What are the functions of IL-8?

A
  • Chemoattractant of neutrophils
  • Upregulates endothelial adhesion molecules (selectins)
49
Q

Which chemokine promotes neutrophil migration?

A
  • IL-8
50
Q

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

A

MAC-I
LFA-I

51
Q

Which tight adhesive molecules are found on the endothelium to interact with migrating neutrophils (2)?

A
  • ICAM-I
  • 2 ligands
52
Q

Which molecules foster transcellular interactions for neutrophils?

A
  • Platelet endothelial cell adhesion molecule (PECAM)
  • Junctional adhesion molecule (JAM)
53
Q

Where does the majority of leukocyte transmigration occur?

A
  • Post-capillary venules
54
Q

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

Diapedesis: The movement of neutrophils from the circulation into the tissues

A
  • CD99
55
Q

What is the function of CD99?

A
  • Upregulates laminin binding integrin
56
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 latelet endothelial cell adhesion molecule (PECAM) interactions on both cells
57
Q

Where do leukocytes transmigrate into (2)?

A
  • Tunica intima

AND

  • Subendothelial space
58
Q

What is found in the subendothelial space that assisst leukocyte migration?

A

Extracellular matrix of proteoglycans and lipids

59
Q

What is the effect of increasing endothelial permeability in the pathogenesis of atherosclerosis (2)?

A
  1. Lipoproteins pass through the fenestrations into the subendothelial space
  2. Macrophages transmigrate into the subendothelial space, detecting LDLs via scavenger receptors
60
Q

Which type of macrophage receptors detect lipoproteins?

A
  • Scavenger receptors
61
Q

What forms foam cells?

A
  • Oxidised lipoproteins phagocytosed by macrophages
62
Q

Which areas potentiate atheroma formation (2)?

A
  • Curvatures
  • Bifurcations

Ascending aorta and the aortic bifurcation of the abdominal aorta

Result in non-uniform haemodynamic forces, potentiating the probability of atheroma formation

63
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
64
Q

What is laminar flow?

A
  • Blood flows in discrete current lines with minimal interference with each other
65
Q

What are the 3 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
66
Q

When is shear stress high on the endothelium?

A
  • During laminar flow
67
Q

What happens to shear stress during turbulent flow?

A
  • Blood flow is distributed with nonuniform and irregular distribution of low wall shear stress
68
Q

What does laminar flow promote in the endothelium (3)?

A
  • Endothelial survival
  • Inhibition of Smooth Muscle Cell proliferation
  • Nitric oxide (NO) production (Vasodilator)
69
Q

What happens to nitric oxide production in turbulent flow?

A
  • Decreases NO production
70
Q

What happens to smooth muscles in turbulent flow?

A
  • Smooth muscle cell proliferation

Proliferation: rapid reproduction of a cell, part, or organism

71
Q

What type of environment is maintained by laminar flow?

A
  • High shear stress exerted onto the endothelium by laminar flows maintains an anti-thrombotic and anti-inflammatory environment
72
Q

What does turbulent flow promote in the endothelium (5)?

A
  • Thrombosis, inflammation (leukocyte adhesion)
  • Endothelial apoptosis
  • Smooth Muscle Cell proliferation
  • Loss of Nitric oxide (NO) production
73
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)
74
Q

What effect is exerted by NO on platelets?

A
  • Anti-thrombotic, reduces platelet activation.
75
Q

What effect does NO have on the vessels?

A
  • Dilation of blood vessels
76
Q

What effect does NO have on superoxides?

A
  • NO reduces the release of superoxide radicals from macrophages and neutrophils
77
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
  • Reduces oxidation of LDL cholesterol
78
Q

What is the janus paradox in angiogenesis?

A
  • Angiogenesis within the vaso vasorum of the adventitia promotes plaque formation

Vs

  • Revascularisation uses the principle of angiogenesis for therapeutic treatment of post-ischaemic coronary arteries
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 (3)?

A
  • Embryonic development
  • Menstural cycle
  • Wound healing
81
Q

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

A
  • Revascularisation

Phase 1b - Cardiovascular & Respiratory Medicine (21 decks)

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