Cardio - Vascular Endothelium

Question 1

What proportion of endothelial cells make up microvasculature?

Answer 1

98%

Question 2

What are the 3 general layers of blood vessels?

Answer 2

→ tunica adventitia
→ tunica media
→ tunica intima

Question 3

What blood vessels are the exceptions to the 3 layer model?

Answer 3

→ capillaries

→ venules

Question 4

What is the tunica adventitia?

Answer 4

→ outermost layer

→ vasa vasorum, nerves

Question 5

What is the tunica media?

Answer 5

→ middle layer
→ smooth muscle cells
→ with external elastic membrane

Question 6

What is the tunica intima?

Answer 6

innermost layer:
→ internal elastic membrane
→ lamina propria (smooth muscle and connective tissue
→ basement membrane
→ endothelium

Question 7

What are capillaries + venules made of?

Answer 7

→ formed only by endothelium
→ supported by some mural cells (pericytes)
→ basement membrane

Question 8

What is the function of capillaries?

Answer 8

→ where the exchanges of nutrients and oxygen between blood and tissues occur
→ Microvascular endothelium promotes tissue homeostasis

Question 9

How is the microvascular endothelium important in tissue homeostasis?

Answer 9

source of angiocrine factors required for the

maintenance of tissue homeostasis + organ regeneration

Question 10

What are angiocrine factors?

Answer 10

molecules found in blood vessels’ endothelial cells that can stimulate organ-specific repair activities in damaged or diseased organs

Question 11

Is all microvasculature the same?

Answer 11

→ NO
→ blood vessels are heterogenic
→ Endothelial cells and microvasculature have organotypic (tissue-specific) properties and expression profiles

Question 12

What is the function of endothelial cells in the vascular system?

Answer 12

→ acts as a vital barrier separating blood from tissues
→ Very extensive: surface area > 1000 m2; weight >100 g
→ Endothelial cells are very flat, about 1-2 μm thick and 10-20 μm in diameter
→ formed by a monolayer of endothelial cells, one cell deep (contact inhibition)
→ endothelial cells live a long life and have a low proliferation rate (unless new vessels are required: angiogenesis)
→ Endothelial cell regulate essential functions of blood vessels

Question 13

What functions does the endothelium control?

Answer 13

→ vascular tone
→ angiogenesis
→ permeability
→ inflammation
→ haemostasis + thrombosis

Question 14

How does endothelium contribute to angiogenesis?

Answer 14

produces matrix products:
→ fibronectin
→ laminin
→ collagen
→ proteoglycans
→ proteases
produces growth factors:
→ insulin like growth factor
→ transforming growth factor
→ colony stimulating growth factor

Question 15

How does endothelium contribute to thrombosis and haemostasis?

Answer 15

produces anti-thrombotic factors:
→ prostacyclin
→ thrombomodulin
→ antithrombin
→ plasminogen activator
→ heparin
produces pro-coagulant factors:
→ von Willebrand factor
→ thromboxane A2
→ thromboplastin
→ Factor V
→ platelet activating factor
→ plasminogen activator inhibitor

Question 16

How does endothelium contribute to vascular tone?

Answer 16

produces vasodilator factors:
→ nitric oxide
→ prostacyclin
produces vasoconstriction factors:
→ ACE
→ thromboxane A2
→ leukotrienes
→ free radicals
→ endothelin

Question 17

How does endothelium contribute to inflammation?

Answer 17

adhesion molecules:
→ ICAMs
→ VCAM
→ selectins
inflammatory mediators:
→ interleukins 1, 6, 8
→ leukotrienes
→ MHC II

Question 18

What is the contact inhibition that endothelium displays?

Answer 18

once in contact with other endothelial cells, cells stop growing and remain 3D

Question 19

What is the resting state of the endothelium?

Answer 19

by default:
→ anti-thrombotic
→ anti-inflammatory
→ anti-proliferative

Question 20

What does the activated endothelium state promote?

Answer 20

turned on by tiggers
→ pro-inflammatory
→ pro-angiogenic
→ pro-thrombotic

Question 21

What are the 3 steps in the pathogenesis of atherosclerosis, in response to injury?

Answer 21

→ endothelial dysfunction
→ fatty-streak formation
→ formation of advanced, complicated lesion

Question 22

What is involved in endothelial dysfunction?

Answer 22

→ endothelial permeability
→ leukocyte migration
→ endothelial adhesion
→ leukocyte adhesion

Question 23

What is involved in fatty-streak formation?

Answer 23

→ smooth muscle migration
→ foam-cell formation
→ T-cell activation
→ adherence + aggregation of platelets
→ adherence + entry of leukocytes

Question 24

What is involved in the formation of an advanced + complicated lesion?

Answer 24

→ macrophage accumulation
→ formation of necrotic core
→ fibrous-cap formation
→ angiogenesis

Question 25

What are the stimuli + risk factors for endothelial dysfunction?

Answer 25

→ hypercholesterolaemia (oxidatively modified lipoproteins)
→ Diabetes Mellitus
→ Hypertension
→ Sex hormonal imbalance
→ Ageing
→ Oxidative Stress
→ Proinflammatory Cytokines
→ Infectious Agents
→ Environmental Toxins
→ Haemodynamic forces

Question 26

What are the 4 mechanisms of endothelial dysfunction?

Answer 26

→ leukocyte recruitment
→ permeability
→ shear stress
→ angiogenesis

Question 27

What does the leukocyte adhesion cascade involve?

Answer 27

→ capture of leukocyte
→ leukocyte rolls along endothelium, slows then arrests
→ adhesion strengthens + spread, leads to intravascular crawling
→ eventually leads to paracellular or transcellular migration

Question 28

When + how does leukocyte recruitment occur in venules / capillaries?

Answer 28

→ recruitment normally happens during inflammation

→ leukocytes adhere to endothelium of post-capillary venules + transmigrate to tissues

Question 29

What is the difference between capillary and post-capillary venules?

Answer 29

similar structure but post-capillary venules contain more pericytes

Question 30

How does leukocyte recruitment occur in atherosclerosis?

Answer 30

→ leukocytes adhere to activated endothelium of large arteries + get stuck in subendothelial space
→ Monocytes migrate into the subendothelial space, differentiate into macrophages + become foam cells

Question 31

What are the consequences of increased permeability for endothelium?

Answer 31

leakage of plasma proteins through junctions into endothelial space

Question 32

How does vascular permeability + leukocyte recruitment lead to foam cell formation?

Answer 32

→ vascular permeability : allows lipoproteins to slip through endothelium into sub-endothelial space
→ leads to being trapped + they bind to proteoglycans, becoming oxidised
→ leukocyte recruitment : recruitment of macrophages causes them to consume oxidised lipoproteins
→ macrophages die + form foam cells

Question 33

Where do atherosclerosis plaques preferentially form in vasculature?

Answer 33

bifurcations + curvatures in the vascular tree

Question 34

Why does atherosclerosis occur at particular points in vasculature?

Answer 34

→ flow patterns and hemodynamic forces are not uniform in the vascular system
→ straight parts of the arterial tree = laminar blood flow + wall shear stress is high and directional
→ branches and curvature = blood flow is disturbed with nonuniform and irregular distribution of low wall shear stress

Question 35

What does laminar blood flow promote?

Answer 35

• anti-thrombotic, anti-inflammatory factors
• endothelial survival
• Inhibition of SMC proliferation
• Nitric oxide (NO) production

Question 36

What does disturbed blood flow promote?

Answer 36

• Thrombosis, inflammation (leukocyte adhesion)
• endothelial apoptosis
• SMC proliferation
• Loss of Nitric oxide (NO) production

Question 37

What are the functions of nitric oxide in the CV system?

Answer 37

→ reduces oxidation of LDL cholesterol
→ vasodilator
→ reduces platelet activation
→ inhibits monocyte adhesion
→ reduces release of superoxide radicals
→ reduces proliferation of SMC in vessel wall

Question 38

What processes is angiogenesis essential for?

Answer 38

→ embryonic development
→ menstrual cycle
→ wound healing
→ therapeutic angiogenesis prevents damage post-ischemia

Question 39

What are the consequences of angiogenesis?

Answer 39

promotes plaque growth in atherosclerosis

Question 40

What significance does thrombosis and coagulopathy have in COVID?

Answer 40

• Both venous and arterial thrombi frequent in COVID19 patients
• Incidence unknown; variability in reports and data analysis
• Coagulopathy (increased D-Dimers, Fibrinogen) correlates with poor prognosis
• Anti-thrombotic therapy recommended in all hospitalised patients (recommendation under review)

Question 41

How does COVID affect coagulapthy?

Answer 41

• COVID infection → cytokine storm → endothelial activation → procoagulant switch

Question 42

What are the 2 possible mechanisms of COVID affecting endothelial cells?

Answer 42

→ “cytokine storm” secondary to SARS-CoV2 infection causes endothelial damage
→ SARS-CoV2 enters endothelial cells and causes direct damage