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Endothelium and Nitric Oxide in CVD Flashcards

1
Q

In which patients are prognostic biomarkers used?

A

Those with overt disease

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2
Q

In which patients are diagnostic biomarkers used?

A

Those who are suspected to have disease

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3
Q

When is screening used?

A

To assist in the care of patients who have no apparent disease

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4
Q

What is the precursor to all cardiovascular disease?

A

Damage to the endothelium

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5
Q

What is the endothelium?

A

Internal lining of all blood vessels

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6
Q

Why is damage to the endothelium a precursor to all CVD?

A

It regulates a number of important pathways that contribute to CVD

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7
Q

True or false
The endothelium detects the direction of blood flow?

A

True

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8
Q

How does endothelium detect the direction of blood flow?

A

Through its mechanoreceptors

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9
Q

How does the endothelium maintain blood flow?

A

Through autoregulation

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10
Q

What are the two types of chemicals that are released from the endothelium?

A

Vasodilators and vasoconstrictors

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11
Q

Examples of vasodilators released from the endothelium

A

Endothelium derived relaxing factor (nitric oxide)
Prostaglandins (PGI2, PGE2)
Endothelium derived hyperpolarising factor (CO)

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12
Q

Examples of vasoconstrictors released from the endothelium

A

Endothelin
Prostanoids (thromboxane, PGG2, PGH2)

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13
Q

How does the endothelium maintain vascular health?

A

Via dilation
Anti-thrombotic
Anti-inflammatory
Anti-oxidant

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14
Q

How is nitric oxide produced by the endothelium?

A

Acetylcholine reacts with the endothelium to produce nitric oxide

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15
Q

What does nitric oxide bind to when it is released from the endothelium?

A

It binds to haemoglobin very quickly

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16
Q

What catalyses the production of nitric oxide?

A

Nitric oxide synthase

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17
Q

What is NOS I?

A

Neuronal NOS (nNOS)

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18
Q

Where is NOS I found?

A

Neurons

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19
Q

What is NOS II?

A

Inducible NOS (iNOS)

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20
Q

Where is NOS II found?

A

Macrophages, neutrophils, fibroblasts, vascular smooth muscle cells, endothelial cells

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21
Q

In what situations does NOS II react?

A

Where inflammation and infection has a role

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22
Q

What is NOS III?

A

Endothelial NOS (eNOS)

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23
Q

Where is NOS III found?

A

Endothelial cells, cardiomyocytes, osteocytes, osteoblasts

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24
Q

Which NOS produces the most NO?

A

NOS II

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25
Which NOS is the one that is produced all the time without activation?
NOS III
26
What is the main precursor of NOS?
L-arganine
27
Examples of tests of endothelial function
Brachial artery catheterisation Brachial artery flow mediated dilatation Laser doppler imaging Endothelium peripheral artery tone Blood markers of endothelial activation Markers of inflammation Markers of coagulation/fibrinolysis
28
Why do you need to stimulate vessels to measure endothelial function
For nitric oxide to kick in
29
Ways in which endothelial function can be stimulated
Vasoactive chemicals (ACh, bradykinin) Ischaemia and post occlusive reactive hyperaemia Local heating
30
Endothelial function is maintained/impaired in diabetes
Impaired
31
Higher body fat results in more/less impairment in endothelial function
More
32
Relationship between breastfeeding and endothelial function?
Longer you breastfeed the better your endothelial function
33
A 1% improvement in endothelial function leads to a __% decrease in risk of CV events?
13% decrease
34
Lifestyle improvements that can be made to improve endothelial function?
Improve diet Quit smoking Increase exercise Weight loss
35
Nitric oxide is scavenged by free radicals to form what?
OONO- (peroxinitrite)
36
Peroxinitrite combines with what to activate guanlyate cyclase in VSMC to produce cycli GMP?
Oxyhaemoglobin
37
How does cyclin GMP lower intracellular calcium?
By increasing SERCA uptake into intracellular stores in VSMC
38
Indirect effects of NO
Inhibits PDE Inhibits endothelin I Inhibits renin release
39
True or false: GTN was first used to manufacture explosives
True
40
NO donor drug examples
Sodium nitroprusside Diethylmine NO and diethylmenetriamine NO S-nitrosothiols
41
Examples of CV agents that modulate endogenous NO bioactivity
Statins ACEi CCB Beta blockers Phosphodiesterase inhibitors
42
Examples of inhibitors of NO synthesis
ADMA - naturally occuring Arginine analogues
43
Examples of NO synthesis
ADMA - naturally occurring Arginine analogues
44
How do endothelial cells detect foreign pathogens?
Via TOL-like receptors and danger-related signals in the bloodstream
45
Engagement of TOL-like receptors controls what?
Cytokine production in atherosclerosis
46
Deletion of TLRs does what?
Prevents atherosclerosis
47
Healthy arteries express low/high levels of TLR2 and TLR4
Low
48
What type of TLR signalling is necessary for the exacerbation of human phenotypes?
TLR-MyD88
49
What is indicative of endothelial dysfunction?
Loss of ability of endothelium to produce NO and impaired vascular tone
50
What is probably the easiest way to measure endothelial function?
NO production
51
Invasive ways to measure endothelial function
Quantitative coronary angiography Intravascular ultrasound Infusion of vasoactive substances
52
Disadvantages of invasive methods of assessing endothelial function?
Expensive, invasive, difficult to perform, operator dependent
53
Non-invasive methods of assessing endothelial function
Flow mediated dilatation Laser doppler flowtometry Laser doppler imaging/laser speckle
54
Blood biomarkers used to assess endothelial function
ICAM VCAM E-selectin NO
55
How is FMD carried out?
By using an ultrasound scan on a major artery (usually brachial)
56
What does FMD show in the vessel wall?
Real time images showing: - Vessel diameter - Endothelial/smooth muscle thickness - Changes in vessel diameter in response to stimuli
57
What physical stimulation can FMD be coupled to?
Sheer stress - post-occlusive hyperaemia
58
How can endothelial independent vasodilation be evaluated in FMD?
Through GFN (NO donor)
59
Advantages of FMD
Non-invasive NO dependent Fully validated and well-established Brachial artery is a suitable surrogate for coronary circulation
60
Disadvantages of FMD
Requires extensive training High inter-operative variability Expensive equipment
61
Assessment techniques of skin microcirculation
Thermography Laser doppler flowmetry/imaging Laser speckle contrast imaging Capillaroscopy Peripheral arterial tonometry
62
Which part of the body does microvascular assessment of endothelial function use?
Forearm
63
What does laser doppler flowmetry do?
Measures skin blood flow non-invasively with a laser beam
64
In laser doppler flowmetry, what gives us an indicator of blood flow?
The speed at which blood is moving Red/yellow means blood flow is faster
65
Examples of stimuli that laser speckle contrast imaging can be applied to
Local heating/cooling Post occlusive reactive hyperaemia Pressure induced vasodilation Vasoactive chemicals
66
Describe the process of iontophoresis
Electromagnetic chambers placed on forearm (one with ACh and one with sodium nitroprusside) Scan for baseline Current applied Transports drugs in solution across intact skin by electrical current
67
Advantages of laser imaging
Easy to use Non-contact Not operator dependent Measures microcirculation specifically
68
Disadvantages of laser imaging
Depth of detection uncertain Lack of standardisation Spatial heterogeneity with single point imaging
69
What is EndoPat?
Peripheral artery tonometry Involves a device placed on finger to measure endothelial function and looks at ratio of occluded arm to non-occluded arm

CVDM (16 decks)

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