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Vascular Endothelium Flashcards

(83 cards)

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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
Which inflammatory mediators are secreted by the endothelium?
IL-1, 6, 8 Leukotrienes MHC-II
26
What are the four main functions of the endothelium?
Angiogenesis Inflammation Vascular tone and permeability Thrombosis and haemostasis
27
Which type of factor is endothelin?
Vasoconstricting factor
28
Which type of factor is thromboxane A2?
Vasoconstricting factor
29
What are the vasoconstricting factors released by the endothelium?
``` Angiotensin-Converting Enzymes (ACE) Thromboxane A2 Leukotrienes Free radicals Endothelin ```
30
What are the two vasodilator factors released by the endothelium?
Nitric oxide | Prostacyclin
31
What are the procoagulant factors that are released by the endothelium?
* Von Willebrand factor * Thromboxane A2 * Thromboplastin * Factor V * Platelet activating factor * Plasminogen activator inhibitor
32
What are the anti-thrombotic factors released by the endothelium?
• Prostacyclin, | thrombomodulin, antithrombin, PA heparin.
33
What is the first step of the pathogenesis of atherosclerosis?
Increased endothelial permeability to lipoproteins and plasma constituents mediated by nitric oxide, prostacyclin, platelet derived growth factor and endothelin.
34
Which molecules are upregulated by leukocytes that promote adhesion to the endothelium?
Leukocyte adhesion molecules: L-selectin Intregrins and platelet endothelial cell adhesion molecule
35
Which molecules are upregulated by endothelial cells that promote leukocyte adhesion
Endothelial adhesion molecules E and P-selectin
36
Which molecules promote the migration of leukocytes into the artery wall?
``` Mediated by low-density lipoprotein MCP-I IL-8 Osteopontin M-CSF ```
37
Which molecules are released by macrophages which oxidise LDLs?
Free oxygen radicals
38
The phagocytosis of OxLDLs by macrophages forms what type of cell?
Foam cell
39
Fatty streak accumulation within the tunica media induces a fibrotic repair process forming what?
A fibrous cap
40
What is ultimately formed due to foam cell formation within the tunica media?
A necrotic core formed from leukocytes , lipids and debris
41
Which factors promote macrophage migration into the sub-endothelium?
MCP-I, MCSF and oxidised low density lipoprotein
42
What does the necrotic core represent?
Represents the results of apoptosis and necrosis, increased proteolytic activity and lipid accumulation
43
What factors contribute towards endothelial cell dysfunction?
Hyperchoelsterolemia Diabetes mellitus/metabolic syndrome Hypertension sex-hormonal imbalance Ageing Oxidative stress Pro-inflammatory cytokines infectious agents Environmental toxins haemodynamic forces
44
What are the four stages of the pathogenesis of atherosclerosis?
1. Leukocyte recruitment 2. Permeability 3. Shear stress 4. Angiogenesis
45
Which chemokine promotes neutrophil migration?
IL-8
46
Which inflammatory cell releases IL-8?
Macrophage
47
What are the functions of IL-8?
Chemoattractant of neutrophils Upregulates endothelial adhesion molecules (selectins)
48
What are the first stages of neutrophil migration?
Rolling and adhesion occurs as neutrophils establish reversible binding between selectins on the endothelial surface and carbohydrate ligands.
49
Which tight adhesive molecules are found on neutrophils and interact with the endothelium?
MAC-I | LFA-I
50
Which tight adhesive molecules are found on the endothelium to interact with migrating neutrophils?
ICAM-I and 2 ligands
51
What is diapedesis?
The movement of neutrophils from the circulation into the tissues
52
Which molecules foster transcellular interactions for neutrophils?
PECAM and JAM interactions
53
Where does the majority of leukocyte transmigration occur?
Post-capillary venules
54
What surrounds the capillary?
Basement membrane and pericapillary cells (pericytes)
55
Which CD marker is produced by endothelial cells and contribute to diapedesis?
CD99
56
What is the function of CD99?
Upregulates laminin binding integrin
57
How do neutrophils transmigrate into tissues?
* 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
Where do leukocytes transmigrate into?
Tunica intima and subendothelial space
59
What is found in the subendothelial space?
Extracellular matrix of proteoglycans and lipids
60
What is the effect of increasing endothelial permeability and atherosclerosis?
Lipoproteins pass through the fenestrations into the subendothelial space. Macrophages transmigrate into the subendothelial space, detecting LDLs via scavenger receptors
61
Which type of macrophage receptors detect lipoproteins?
Scavenger receptors
62
What forms foam cells?
Oxidised lipoproteins within macrophages
63
Which areas potentiate atheroma formation?
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
How do plaques affect shear stress?
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
What is laminar flow?
Blood flows in discrete current lines with minimal interference with each other
66
What are the three characteristics of laminar flow?
* 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
When is shear stress high on the endothelium?
During laminar flow
68
What happens to shear stress during turbulent flow?
In branches and curvatures, blood flow is distributed with nonuniform and irregular distribution of low wall shear stress.
69
What does laminar flow promote?
factors • Endothelial survival • Inhibition of Smooth Muscle Cell proliferation • Nitric oxide (NO) production (Vasodilator)
70
What happens to nitric oxide production in turbulent flow?
Decreases NO production
71
What happens to smooth muscles in turbulent flow?
Smooth muscle cell proliferation
72
What type of environment is maintained by laminar flow?
High shear stress exerted onto the endothelium by laminar flows maintains an antithrombotic and anti-inflammatory environment.
73
What happens during turbulent flow?
* Thrombosis, inflammation (leukocyte adhesion) * Endothelial apoptosis * Smooth Muscle Cell proliferation * Loss of Nitric oxide (NO) production
74
What is the function of nitric oxide released by endothelial cells on lipoproteins?
NO reduces the oxidation of LDL cholesterol (major component of plaque)
75
What effect is exerted by NO on platelets?
Anti-thrombotic, reduces platelet activation.
76
What effect does NO have on the vessels?
Dilation of blood vessels
77
What effect does NO have on superoxides?
NO reduces the release of superoxide radicals from macrophages and neutrophils
78
What are the 6 main functions of nitric oxide?
* 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
Which factor stimulates angiogenesis in hypoxic conditions?
Hypoxia inducible factor stimualtes epo production and potentiates activity of angiogenesis.
80
What are the benefits of angiogenesis?
Embryonic development, menstural cycle and wound healing
81
What is the janus paradox?
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
What is the therapeutic treatment of post-ischaemic coronary arteries?
Revascularisation
83
What is a marker of endothelial injury?
Circulating endothelial cells

BRS 2 (62 decks)

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