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CVS > 18. Vascular Endothelium > Flashcards

18. Vascular Endothelium Flashcards

1
Q

What is the atherosclerosis timeline?

A

1) Foam cells
2) Fatty streak
3) Intermediate lesion
4) Atheroma
5) Fibrous plaque
6) Complicated lesion/rupture

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2
Q

What are the 3 layers of the blood vessels?

A
  • Tunica intima - endothelium
  • Tunica media - VSMCs
  • Tunic adventitia - Vasa Vasorum (small blood vessels), Nerves
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3
Q

What is contact inhibition?

A

Regulatory mechanism in endothelial cells that makes sure they form a monolayer

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4
Q

What 4 main things do the functions of endothelial cells involve?

A
  • Inflammation
  • Vascular Tone and Permeability
  • Angiogenesis
  • Thrombosis and Haemostasis
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5
Q

What state do resting endothelial cells maintain compared to someone who has cut themselves?
(in terms of inflammation, thrombosis and angiogenesis)

A

Normal
• Anti-inflammatory
• Anti-thrombotic
• Anti-angiogenic

Cut
• Pro-inflammatory
• Pro-thrombotic
• Pro-angiogenic

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6
Q

In which part of the endothelium do leukocytes normally adhere to?

A

Post-capillary venules

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7
Q

In which part of the endothelium do leukocytes adhere to during atherosclerosis?

A

Activated endothelium of large arteries

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8
Q

Why does the activated endothelium attract leukocytes?

A
  • Normally the selectins and integrins on leukocytes are turned off
  • Some are turned on but don’t have complementary receptors on the endothelium
  • Inflammation => activated endothelium => starts to express ligands
  • Selectins on leukocyte weakly interacts with the endothelium
  • Integrin high affinity state - strong binding
  • Adhesion and transmigration
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9
Q

What is V-cadherin?

A

A protein present at endothelial junctions

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10
Q

How do endothelial cell membranes bind to each other?

A
  • Homophilic attraction
  • Binding membrane creates a zipper
  • Junctions can unzip allowing substances to pass
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11
Q

What happens to babies born with integrin mutations?

A
  • Live for around 3 months
  • Unable to deal with infection
  • Mutations in molecules are not compatible with life
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12
Q

What surrounds the endothelial cells in the capillary and post-capillary venule?

A
  • Basement membrane
  • Pericapillary cells (perycites)
  • More pericytes in the post-capillary venule
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13
Q

How do leukocytes pass through the basement membrane?

A
  • Enzymes used to break it down in its path, allowing them to pass through
  • Thick layer in coronary artery or aorta stops it from passing => atherosclerosis
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14
Q

What is a positive protective signal?

A
  • Laminar flow sensed by the endothelium

* Production of protective molecules e.g. NO and anticoagulants, is triggered

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15
Q

What does turbulent flow promote?

A
  • Coagulation
  • Leukocyte adhesion
  • VSMC proliferation
  • Endothelial apoptosis
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16
Q

What are epigenetics?

A

Functionally relevant, inheritable changes to the genome that do not involve a change in the nucleotide sequence, which affect gene expresison

17
Q

How do epigenetics play a role in the affect of flow on atherogenesis?

A

• Laminar flow

  • downregulates the expression of DNA methyltransferases (DNMTs)
  • Promoter of antiatherogenic genes remain demethylated
  • Expression enabled => anti-atherogenesis

• Turbulent flow

  • upregulates the expression of DNA methyltransferases
  • Hypermethylation of promoter of antiatherogenic genes
  • Expression repressed => pro-atherogenesis
18
Q

What is angiogenesis?

A

Formation of new blood vessels by sprouting from pre-existing vessels

19
Q

What triggers angiogenesis?

A
  • Tissue becomes hypoxic
  • Releases chemicals which activate existing blood vessels
  • Change in the cells triggered
  • Cells that become a ‘tip cell’ control the formation of a new blood vessel
  • Stabilised blood vessel forms
20
Q

What is The Janus Paradox?

A

Negative side of angiogenesis
• Advanced plaque
• Necrotic debris => hypoxia => angiogenesis from the Vasa Vasorum
• Vasa Vasorum vessels are fragile - more leukocytes will come

Positive side of angiogenesis
• Therapeutic angiogenesis
• Useful when Acute Myocardial Infarction leads to fibrotic tissue where the ischaemia had an impact
• If done quickly - myocardium could be reoxygenated preventing tissue damage and heart failure

21
Q

What is senescence?

A
  • Growth arrest that halts the proliferation of ageing or damaged cells
  • Prevents damaged cells from taking over (mechanism against cancer)
22
Q

What is a negative affect of senescent cells?

A
  • Senescent cells can develop a proinflammatory phenotype
  • Senescence can be induced by cardiovascular risk factors
  • Found in atherosclerotic lesions
23
Q

What does red wine contain and what effect does this have?

A
  • Resveratrol
  • Anti-inflammatory properties on the endothelium
  • Hormetic action - beneficial at lower doses, cytotoxic at higher doses

CVS (21 decks)

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