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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
Q

Which NOS is the one that is produced all the time without activation?

A

NOS III

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26
Q

What is the main precursor of NOS?

A

L-arganine

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27
Q

Examples of tests of endothelial function

A

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

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28
Q

Why do you need to stimulate vessels to measure endothelial function

A

For nitric oxide to kick in

29
Q

Ways in which endothelial function can be stimulated

A

Vasoactive chemicals (ACh, bradykinin)
Ischaemia and post occlusive reactive hyperaemia
Local heating

30
Q

Endothelial function is maintained/impaired in diabetes

31
Q

Higher body fat results in more/less impairment in endothelial function

32
Q

Relationship between breastfeeding and endothelial function?

A

Longer you breastfeed the better your endothelial function

33
Q

A 1% improvement in endothelial function leads to a __% decrease in risk of CV events?

A

13% decrease

34
Q

Lifestyle improvements that can be made to improve endothelial function?

A

Improve diet
Quit smoking
Increase exercise
Weight loss

35
Q

Nitric oxide is scavenged by free radicals to form what?

A

OONO- (peroxinitrite)

36
Q

Peroxinitrite combines with what to activate guanlyate cyclase in VSMC to produce cycli GMP?

A

Oxyhaemoglobin

37
Q

How does cyclin GMP lower intracellular calcium?

A

By increasing SERCA uptake into intracellular stores in VSMC

38
Q

Indirect effects of NO

A

Inhibits PDE
Inhibits endothelin I
Inhibits renin release

39
Q

True or false:
GTN was first used to manufacture explosives

40
Q

NO donor drug examples

A

Sodium nitroprusside
Diethylmine NO and diethylmenetriamine NO
S-nitrosothiols

41
Q

Examples of CV agents that modulate endogenous NO bioactivity

A

Statins
ACEi
CCB
Beta blockers
Phosphodiesterase inhibitors

42
Q

Examples of inhibitors of NO synthesis

A

ADMA - naturally occuring
Arginine analogues

43
Q

Examples of NO synthesis

A

ADMA - naturally occurring
Arginine analogues

44
Q

How do endothelial cells detect foreign pathogens?

A

Via TOL-like receptors and danger-related signals in the bloodstream

45
Q

Engagement of TOL-like receptors controls what?

A

Cytokine production in atherosclerosis

46
Q

Deletion of TLRs does what?

A

Prevents atherosclerosis

47
Q

Healthy arteries express low/high levels of TLR2 and TLR4

48
Q

What type of TLR signalling is necessary for the exacerbation of human phenotypes?

49
Q

What is indicative of endothelial dysfunction?

A

Loss of ability of endothelium to produce NO and impaired vascular tone

50
Q

What is probably the easiest way to measure endothelial function?

A

NO production

51
Q

Invasive ways to measure endothelial function

A

Quantitative coronary angiography
Intravascular ultrasound
Infusion of vasoactive substances

52
Q

Disadvantages of invasive methods of assessing endothelial function?

A

Expensive, invasive, difficult to perform, operator dependent

53
Q

Non-invasive methods of assessing endothelial function

A

Flow mediated dilatation
Laser doppler flowtometry
Laser doppler imaging/laser speckle

54
Q

Blood biomarkers used to assess endothelial function

A

ICAM
VCAM
E-selectin
NO

55
Q

How is FMD carried out?

A

By using an ultrasound scan on a major artery (usually brachial)

56
Q

What does FMD show in the vessel wall?

A

Real time images showing:
- Vessel diameter
- Endothelial/smooth muscle thickness
- Changes in vessel diameter in response to stimuli

57
Q

What physical stimulation can FMD be coupled to?

A

Sheer stress - post-occlusive hyperaemia

58
Q

How can endothelial independent vasodilation be evaluated in FMD?

A

Through GFN (NO donor)

59
Q

Advantages of FMD

A

Non-invasive
NO dependent
Fully validated and well-established
Brachial artery is a suitable surrogate for coronary circulation

60
Q

Disadvantages of FMD

A

Requires extensive training
High inter-operative variability
Expensive equipment

61
Q

Assessment techniques of skin microcirculation

A

Thermography
Laser doppler flowmetry/imaging
Laser speckle contrast imaging
Capillaroscopy
Peripheral arterial tonometry

62
Q

Which part of the body does microvascular assessment of endothelial function use?

63
Q

What does laser doppler flowmetry do?

A

Measures skin blood flow non-invasively with a laser beam

64
Q

In laser doppler flowmetry, what gives us an indicator of blood flow?

A

The speed at which blood is moving
Red/yellow means blood flow is faster

65
Q

Examples of stimuli that laser speckle contrast imaging can be applied to

A

Local heating/cooling
Post occlusive reactive hyperaemia
Pressure induced vasodilation
Vasoactive chemicals

66
Q

Describe the process of iontophoresis

A

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
Q

Advantages of laser imaging

A

Easy to use
Non-contact
Not operator dependent
Measures microcirculation specifically

68
Q

Disadvantages of laser imaging

A

Depth of detection uncertain
Lack of standardisation
Spatial heterogeneity with single point imaging

69
Q

What is EndoPat?

A

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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