Vascular endothelium Flashcards

1
Q

what is the basic structure of blood vessels?

A
  • 3 layers:
    • Tunica adventitia
    • Tunica media
    • Tunica intima
  • Capillaries and venules formed only by endothelium.
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2
Q

what are capillaries and venules supported by?

A

some mural cells (pericytes) and basement membrane

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3
Q

what is in the tunica adentitia?

A

vasa vasorum

nerves

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4
Q

what is in the tunica media?

A

smooth muscle cells

external elastic membrane

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5
Q

what is in the tunica intima?

A

endothelium

internal elastic membrane

lamina propria (smooth muscle and connective tissue)

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6
Q

what do capillaries do?

A

exchange nutrients and oxygen between blood tissues?

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7
Q

what does microvasculature endothelium promote?

A

tissue homeostasis

sources angiocrine factors- maintenance tissue homeostasis and organ regeneration

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8
Q

what can damage to microvasculature endothelium cause?

A

organ dysfunction

  • Ischaemia
  • Chronic inflammatory diseases
  • Cancer
  • Diabetes
  • Atherosclerosis
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9
Q

what is the heterogeneity of blood vessels?

A

not all blood vessels are the same

there is vascular and endothelial heterogeneity

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

function and phenotype depends on location

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10
Q

what is the use of endothelial cells?

A

barrier separating blood from tissues

regulate essential functions of blood vessels

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11
Q

what is the composition of endothelial cells?

A
  • Very extensive, surface area >100m2
  • Flat- 1-2um thick and 10-20um diameter
  • Formed by a monolayer of endothelial cells, one cell deep (contact inhibition)
  • long life and low proliferation rate
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12
Q

what is contact inhibition?

A

2 cells form a junction results in cell inhibiting growth

only allows growth in 2 directions

done only by endothelial and epithelial cells

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13
Q

what are the main functions of resting epithelium?

A

anti-inflammatory

anti-thrombotic

anti-proliferative

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14
Q

what are the actions of activated endothelium?

A

pro-inflammatory

pro-thrombotic

pro-angiogenic

leukocyte recruitment

increases permeability

this all contributes to atherosclerotic profile

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15
Q

what can cause an activated endothelium?

A

mechanical stress

inflammation

high BP

OxLDL

high glucose

viruses

smoking

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16
Q

what is the pathogenesis of atherosclerosis?

A
  1. endothelial dysfunction
  2. fatty steak formation
  3. formation of an advanced, complicated lesion of atherosclerosis
17
Q

what happens during endothelial dysfunction?

A

increase in endothelial permeability and endothelial adhesion

leukocyte migration and adhesion

18
Q

what happens during fatty-streak formation?

A

smooth muscle migration

T-cell activation

adherence and aggregation of platelets

adherence and entry of leukocytes

causes foam cell formation

19
Q

what happens during formation of an advanced, complicated lesion?

A

macrophage accumulation

angiogenesis

formation of a necrotic core with fibrous cap

20
Q

what are the triggers for atherogenesis?

A
21
Q

what is the overall atherosclerosis pathogenesis mechanisms?

A
  1. Leukocyte recruitment
  2. Permeability
  3. Sheer stress
  4. Angiogenesis
22
Q

what happens during leukocyte recruitment?

A
  • recruitment of blood leukocytes into tissue takes place during inflammation
  • Leukocytes adhere to endothelium of post-capillary venules and transmigrate into tissues

In atherosclerosis:

  • Leukocytes adhere to activated endothelium of large arteries
  • Get stuck in subendothelial space
  • Monocytes migrate into subendothelial space
  • Differentiate into macrophages to become foam cells
23
Q

what are capillaries?

A

endothelial cells surrounded by basement membrane and pericapillary cells (pericytes)

24
Q

what is the difference between capillary and post-capillary venule?

A

a structure similar to capillaries but more pericytes

25
Q

how does permeability affect atherosclerosis?

A
  • Endothelium regulates flux of fluids and molecules from blood to tissue and vice versa
  • Increased permeability= leakage plasma proteins through junctions into the subendothelial space
  • Lipoproteins go through leaky junction and bind to proteoglycans
    • Get oxidated in subendothelial space
  • Microphages enter and combine with oxidised lipoproteins to form foam cells à early plaque formation
26
Q

how does sheer stress contribute to atherosclerosis?

A
  • Atherosclerosis occurs preferentially at bifurcations and curvatures of vascular tree
  • Flow patterns and hemodynamic forces are not uniform in the vascular system
  • Laminar blood flow= straight parts of arterial tree à wall sheer stress high and directional
  • Disturbed (turbulent) blood flow= branches and curvature à non uniform and irregular distribution of low wall shear stress à chronic endothelial activation
27
Q

what are the properties of laminar blood flow?

A

anti-thrombotic

anti-inflammatory

endothelial survival

inhibition of SMC proliferation

Nitric oxide production

28
Q

what does disturbed blood flow promote?

A

thrombosis

inflammation (leukocyte adhesion)

endothelial apoptosis

SMC proliferation

loss nitric oxide production

29
Q

what are the effects of nitric oxide of the vascular endothelium?

A

NO is protective and essential for health of cardiovascular system

reduces oxidation of LDL cholesterol (major component in plaque)

dilates blood vessels

reduces platelet activation

inhibits monocyte adhesion

reduces proliferation of SMC in vessel wall

reduces the release of superoxide radicals

30
Q

what is angiogenesis?

A

formation of new vessels by sprouting from existing vessels

31
Q

what can angiogenesis be initiated by?

A

signalling promoted by hypoxia

32
Q

what is angiogenesis essential for?

A

embryonic development

menstrual cycle

wound healing

33
Q

what is the role of angiogenesis in cardiovascular disease?

A

good and bad

promotes plaque growth

therapeutic angiogenesis promotes damage post ischemia

( induction of angiogenesis downstream of a plaque= revascularize and prevent loss of tissue)

34
Q

what is the role of thrombosis and coagulopathy in COVID19 patients?

A

SARS-CoV2 infection-> cytokine store -> endothelial activation -> procoagulant switch

venous and arterial thrombi frequent -> points to endothelial role

coagulopathy (increase D-dimers, fibrinogen) correlated with poor prognosis

anti-thrombotic therapy recommended in all hospitalised patients