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
2
Q
What is found within the tunica adventitia (2)?
A
- Vaso vasorum
- Nerves
Nerves
3
Q
Which types of fibres form the tunica media (2)?
A
- Smooth muscle cells
- Elastic fibres
4
Q
What is the tunica intima?
A
- Endothelium
5
Q
Which cells support the venule and capillary endothelium?
A
- Mural cells (pericytes)
6
Q
What surrounds the capillary (2)?
A
- Basement membrane
- Pericapillary cells (pericytes)
7
Q
What is the function of the mural cells (pericytes)?
A
- Maintains homeostatic & haemostatic function
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.
9
Q
Which types of proteins are involved in cell adhesion and the formation of the monolayer?
A
E-cadherins
10
Q
Which process arrests cell growth when cells come in contact with each other?
A
- Contact inhibition
11
Q
What are the 3 types of endothelium?
A
- Fenestrated continuous endothelium
- Non-fenestrated continuous endothelium
- Discontinuous
12
Q
Where are fenestrated continuous endothelium found (2)?
A
- Kidney glomerulus
- Gastrointestinal tract
To facilitate filtration and absorption
13
Q
Where are the non-fenestrated continuous endothelium found (4)?
A
- Muscle
- Lung
- Skin
- Blood brain barrier
To regulate diffusion
14
Q
What type of endothelium is found within the liver?
A
- Discontinuous
15
Q
What type of layer is formed by the endothelium?
A
- Monolayer
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
17
Q
Which factor is secreted by the endothelium and mediates platelet adhesion?
A
- Von Willebrand Factor
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
19
Q
Describe the proliferation rate in endothelial cells
A
- Low proliferation rate unless angiogenesis is induced
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
21
Q
Which factors activate the endothelium (7)?
A
- OxLDL
- High glucose
- High blood pressure
- Inflammation
- Mechanical stress
- Viruses
- Smoking
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
23
Q
What is a marker of endothelial injury?
A
Circulating endothelial cells
24
Q
What are the matrix products involved in angiogenesis (5)?
A
- Fibronectin
- Laminin
- Collagen
- Proteoglycans
- Proteases
25
What are the growth factors concerned with angiogenesis (3)?
* **Insulin-like** growth factor
* **Transforming** growth factor
* **Colony stimulating** factor
26
Which adhesion molecules exist on the endothelium and promote neutrophil migration?
* Intercellular adhesion molecule **(ICAM)**
* Vascular cell adhesion molecule **(VCAM)**
## Footnote
Selectins - P-selectin
27
Which inflammatory mediators are secreted by the endothelium (5)?
* IL-1
* IL-6
* IL-8
* Leukotrienes
* MHC-II
28
What are the vasoconstricting factors released by the endothelium (5)?
* Angiotensin-Converting Enzymes **(ACE)**
* **Thromboxane A2**
* **Leukotrienes**
* **Free radicals**
* **Endothelin**
29
Which type of factor is endothelin?
* **Vasoconstricting** factor
30
Which type of factor is thromboxane A2?
* **Vasoconstricting** factor
31
What are the 2 vasodilator factors released by the endothelium?
* **Nitric oxide**
* **Prostacyclin**
32
What are the procoagulant factors that are released by the endothelium (6)?
* **Von Willebrand factor**
* **Thromboxane A2**
* **Thromboplastin**
* **Factor V**
* **Platelet activating factor**
* **Plasminogen activator inhibitor**
33
What are the anti-thrombotic factors released by the endothelium (4)?
* **Prostacyclin**
* **Thrombomodulin**
* **Antithrombin**
* **PA heparin**
34
What are the four stages of the pathogenesis of atherosclerosis?
1. **Leukocyte recruitment**
2. **Permeability**
3. **Shear stress**
4. **Angiogenesis**
35
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.
36
Fatty streak accumulation within the tunica media induces a fibrotic repair process forming what?
* A **fibrous cap**
37
What is ultimately formed due to foam cell formation within the tunica media?
* A **necrotic core** formed from leukocytes , lipids and debris
38
What does the necrotic core represent (3)?
* Represents the **results of apoptosis and necrosis**, **increased proteolytic activity** and **lipid accumulation**
39
Which molecules are upregulated by endothelial cells that promote leukocyte adhesion (2)?
* **E-selectin**
* **P-selectin**
40
Which molecules are upregulated by leukocytes that promote adhesion to the endothelium (3)?
* **L-selectin**
* **Intregrins**
* **Platelet endothelial cell adhesion molecule**
41
Which molecules promote the migration of leukocytes into the artery wall (5)?
* Low-density lipoprotein **(LDL)**
* **MCP-I**
* **IL-8**
* **Osteopontin**
* **M-CSF**
42
The phagocytosis of OxLDLs by macrophages forms what type of cell?
* **Foam cell**
43
Which molecules are released by macrophages which oxidise LDLs?
* **Free oxygen radicals**
44
Which factors promote macrophage migration into the sub-endothelium (3)?
* **MCP-I**
* **MCSF**
* Oxidised low density lipoprotein **(OxLDL)**
45
What is diapedesis?
* The **movement** of **neutrophils** from the **circulation** into the **tissues**
46
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
47
Which inflammatory cell releases IL-8?
**Macrophage**
48
What are the functions of IL-8?
* **Chemoattractant of neutrophils**
* **Upregulates** endothelial adhesion molecules **(selectins)**
49
Which chemokine promotes neutrophil migration?
* **IL-8**
50
Which tight adhesive molecules are found on neutrophils and interact with the endothelium?
**MAC-I**
**LFA-I**
51
Which tight adhesive molecules are found on the endothelium to interact with migrating neutrophils (2)?
* **ICAM-I**
* **2 ligands**
52
Which molecules foster transcellular interactions for neutrophils?
* Platelet endothelial cell adhesion molecule **(PECAM)**
* Junctional adhesion molecule **(JAM)**
53
Where does the majority of leukocyte transmigration occur?
* **Post-capillary venules**
54
Which CD marker is produced by endothelial cells and contribute to diapedesis?
## Footnote
Diapedesis: The movement of neutrophils from the circulation into the tissues
* **CD99**
55
What is the function of CD99?
* **Upregulates laminin binding integrin**
56
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 latelet endothelial cell adhesion molecule **(PECAM)** interactions on both cells
57
Where do leukocytes transmigrate into (2)?
* **Tunica intima**
AND
* **Subendothelial space**
58
What is found in the subendothelial space that assisst leukocyte migration?
**Extracellular matrix** of **proteoglycans** and **lipids**
59
What is the effect of increasing endothelial permeability in the pathogenesis of atherosclerosis (2)?
1. **Lipoproteins pass** through the fenestrations **into the subendothelial space**
1. **Macrophages transmigrate into the subendothelial space**, detecting LDLs via scavenger receptors
60
Which type of macrophage receptors detect lipoproteins?
* **Scavenger receptors**
61
What forms foam cells?
* **Oxidised lipoproteins** **phagocytosed** by **macrophages**
62
Which areas potentiate atheroma formation (2)?
* **Curvatures**
* **Bifurcations**
| Ascending aorta and the aortic bifurcation of the abdominal aorta
## Footnote
Result in non-uniform haemodynamic forces, potentiating the probability of atheroma formation
63
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
64
What is laminar flow?
* Blood flows in **discrete current lines** with **minimal interference** with each other
65
What are the 3 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**
66
When is shear stress high on the endothelium?
* During **laminar** flow
67
What happens to shear stress during turbulent flow?
* Blood flow is distributed with nonuniform and irregular distribution of **low wall shear stress**
68
What does laminar flow promote in the endothelium (3)?
* **Endothelial survival**
* **Inhibition of Smooth Muscle Cell proliferation**
* **Nitric oxide (NO) production** (Vasodilator)
69
What happens to nitric oxide production in turbulent flow?
* **Decreases** NO production
70
What happens to smooth muscles in turbulent flow?
* Smooth muscle cell **proliferation**
## Footnote
Proliferation: rapid reproduction of a cell, part, or organism
71
What type of environment is maintained by laminar flow?
* High shear stress exerted onto the endothelium by laminar flows maintains an **anti-thrombotic** and **anti-inflammatory** environment
72
What does turbulent flow promote in the endothelium (5)?
* **Thrombosis**, **inflammation** (leukocyte adhesion)
* **Endothelial apoptosis**
* **Smooth Muscle Cell proliferation**
* **Loss of Nitric oxide (NO) production**
73
What is the function of nitric oxide released by endothelial cells on lipoproteins?
* **NO reduces the oxidation of LDL cholesterol** (major component of plaque)
74
What effect is exerted by NO on platelets?
* **Anti-thrombotic**, reduces platelet activation.
75
What effect does NO have on the vessels?
* **Dilation** of blood vessels
76
What effect does NO have on superoxides?
* NO **reduces the release of superoxide radicals** from macrophages and neutrophils
77
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**
* **Reduces oxidation of LDL cholesterol**
78
What is the janus paradox in angiogenesis?
* 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
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 (3)?
* **Embryonic** development
* **Menstural** cycle
* **Wound** healing
81
What is the therapeutic treatment of post-ischaemic coronary arteries?
* **Revascularisation**
