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BRS Year 2 > CVR Vascular Endothelium - in health and disease > Flashcards

CVR Vascular Endothelium - in health and disease Flashcards

1
Q

layers of blood vessels (outside to inside)

A
  1. tunica adventitia
  2. tunica media
  3. tunica intima
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2
Q

what travels in the tunica adventitia?

A

vasa vasorum

nerves

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3
Q

what forms the tunica media?

A

smooth muscle cells

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4
Q

whatforms the tunica intima?

A

endothelium

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5
Q

what vessel types are formed only by endothelial cells?

A
  1. capillaries

2. venules

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6
Q

which cells support the endothelial cells that make up capillaries/venules?

A

pericytes (mural cells)

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7
Q

microvascular endothelium promotes what?

A

tissue homeostasis

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8
Q

What is the microvascular endothelium the source of and what is their role?

A

angiocrine factors

Required for tissue homeostasis and organ regeneration

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9
Q

what diseases does dysfunctional endothelium contribute to? (4)

A
  • ischaemia
  • chronic inflammatory diseases
  • cancer
  • diabetes
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10
Q

what contributes to vascular and endothelial heterogeneity?

A

endothelial cells and microvasculature have organotypic (tissue specific) properties and expression profiles

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11
Q

what is contact inhibition?

A

when two cells come together, causing them to stop growing

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12
Q

do endothelial cells have a long life?

A

yes.

And low proliferation rate (unless new vessels required: angiogenesis)

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13
Q

what is the function of endothelial cells?

A

regulate essential functions of blood vessels

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14
Q

What are the essential functions of the endothelium? (5)

A
  • angiogenesis
  • haemostasis and thrombosis
  • inflammation
  • permeability
  • vascular tone
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15
Q

What are factors that lead to an activated endothelium (7)

A
  1. mechanical stress
  2. inflammation
  3. viruses
  4. smoking
  5. high glucose
  6. oxidised LDL
  7. high blood pressure
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16
Q

response to injury model of artherosclerosis

A
  • Endothelial dysfunction results in endothelial activation
  • endothelial permeability increases, leukocyte migration increases, leukocyte adhesion increases
  • leads to foam cell formation
  • fatty streak formation occurs
  • macrophage accumulation, formation of necrotic core and angiogenesis occur - formation of an advanced, complicated lesion of atherosclerosis
17
Q

stages of leucocyte adhesion cascade during inflammation of post-capillary venules (5)

A
  1. capture
  2. activation
    rolling, slow rolling, arrest
  3. adhesion strengthening, spreading
  4. intravascular crawling
  5. paracellular and transcellular transmigration
18
Q

why is the stages of leucocyte adhesion different in atherosclerosis to what happens in post-capillary venules?

A
  • leukocytes are adhering to activated endothelial cells of large arteries and get stuck in the subendothelial space
19
Q

what happens to leucocytes stuck in the subendothelial space?

A

monocytes differentiate into macrophages and become foam cells

20
Q

what leaks through junctions if endothelial cell permeability increases?

A

plasma proteins

21
Q

stages of lipoprotein trapping

leading to fatty streak formation

A
  1. endothelial cells are leaky
  2. lipoproteins leak from vessel
  3. lipoproteins get oxidised by proteoglycans
  4. macrophages engulf these oxidised lipoproteins -> forming foam cells
22
Q

why does artherosclerosis occur preferentially at bifurcation and curvatures of the vascular tree?

A
  • the flow patterns and haemodynamic forces are not uniform in the vascular system
23
Q

what type of blood flow occurs in the straight parts of the arterial tree?

A

laminar - wall shear stress is high and directional

24
Q

what type of blood flow occurs in the branched parts of the arterial tree?

A

turbulent flow - non uniform and irregular distribution of low wall shear stress

25
Q

what does laminar blood flow promote? (4)

A
  • anti-thrombotic and anti-inflammatory factors
  • endothelial survival
  • inhibition of SMC proliferation
  • nitric oxide production
26
Q

What does disturbed blood flow promote?

A

Thrombosis,inflammation
Endothelial apoptosis
SMC proliferation
Loss of Nitric oxide production

27
Q

protective effects of nitric oxide (6)

A
  1. reduced oxidation of LDL cholesterol (major component of plaque)
  2. reduces release of superoxide radicals
  3. dilates blood vessels
  4. Reduces platelet activation
  5. inhibits monocyte adhesion
  6. reduces proliferation of smooth muscle cells in the vessel
28
Q

what physiological processes is angiogenesis necessary for? (3)

A
  1. embryonic development
  2. wound healing
  3. menstrual cycle
29
Q

What are two other important roles of angiogenesis?

A

Promotes plaque growth

Therapeutic angiogenesis prevents damage post- ischaemia

30
Q

stages of endothelial involvement with SARS-CoV2 infection

A

SARS-COV2 infection -> cytokine storm -> endothelial activation -> procoagulant switch (endothelium loses ability to be anticoagulant)

31
Q

types of macrophage scavenger receptors

A

A and B

32
Q

how is arterial Ox-LDL useful?

A

safe clearance,

reverse cholesterol transport

33
Q

What is the main host receptor in covid?

A

ACE2 - not on endothelial cells, but epithelial cells

34
Q

Where do the majority of endothelial cells reside?

A

capillaries

35
Q

Physiologically, in which vessels does leukocyte transmigration occur?

A

In post-capillary venules

Same as capillaries but with more pericytes

36
Q

Which processes promotes early development of atherosclerotic plaques (3)?

A
  1. endothelial activation
  2. permeability
  3. leukocyte adhesion
37
Q

How are endothelial cells structured? (3)

A

Have a large surface area: endothelium is >1000m2
They’re very flat and around 1-2 um thick and 10-20um in diameter
Form a monolayer of endothelial cells which is 1 cell thick (contact inhibition)

38
Q

What are 4 things that an activated endothelium leads to?

A

Thrombosis
Permeability
Senescence
Leukocyte recruitment

39
Q

What are risk factors and stimuli for endothelial cell dysfunction? (10)

A 
Hypercholesterolaemia
Diabetes mellitus/ metabolic syndrome
Hypertension
Sex hormone imbalance
Aging
Oxidative stress
Proinflammatory cytokines
Infectious agents
Environmental toxins
Hydrodynamic forces

BRS Year 2 (110 decks)

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