Vascular Endothelium 2

Question 1

Describe the endothelium of the blood vessels

Answer 1

Single cell layer

Lots of gap junctions for cell-cell communication

Question 2

What are the three layers of the blood vessels (outside->inside)

Answer 2

Tunica adventitia (vasa vasorum, nerves)
Tunica media (smooth muscle cells)
Tunica intima (lamina propria, basement membrane, endothelium)

Question 3

What can endothelium dysfunction lead to

Answer 3

Atherosclerosis

Fatty streak formation and therefore advanced complicate lesion

Question 4

Describe the microcirculation

Answer 4

Endothelial cells surrounded by basement membrane and pericapillary cells

Post-capillary venues - more pericytes

Question 5

What are the functions of the endothelium

Answer 5

Angiogenesis e.g. matrix products and growth factors
Thrombosis & haemostasis e.g. procoagulant factors and antithrombotic factors
Inflammation e.g. Adhesion molecules and inflammatory mediators
Vascular tone permeability e.g. vasoconstricting factors and vasodilator factors

Question 6

Describe leukocyte recruitment in inflammation

Answer 6

Blood leukocytes are recruited into tissues where they adhere to the post-capillary venule endothelium

Question 7

Describe leukocyte recruitment in atherosclerosis

Answer 7

Leukocytes adhere to activated endothelium if large arteries and get stuck in the sub endothelial space (monocytes -> macrophages)

Question 8

What role does angiogenesis play in leukocyte recruitment

Answer 8

Newly formed post-capillary venules at the base of the developing lesions provide a further portal for leukocyte entry

Question 9

Explain the leukocyte adhesion cascade

Answer 9

1. Inflammatory trigger activates the endothelium to express more adhesion molecules
2. Leukocytes roll along the endothelium
3. Leukocytes bind to the adhesion molecules
4. Leukocytes stop
5. Leukocyte passes through the endothelium through small junctions

Question 10

What causes cells to become quiscent

Answer 10

When two dividing cells touch each other, they engage with molecular pathways which cause them to become quiescent.
Endothelial cells rarely divide (not for repair). Therefore they form a monolayer

Question 11

What is an important junction in vascular endothelium

Answer 11

VE-cadherin is a very important junction

Question 12

Describe the permeability of the vascular endothelium

Answer 12

Regulates flux of fluid and molecules from blood to tissues and vice versa
Increased permeability -> leakage of proteins through junctions

Question 13

Describe the changes in permeability which lead to atherosclerosis

Answer 13

Endothelial dysfunction causes an increase in permeability
Activated LDLs pass through and bind to proteoglycans
Oxidation and phagocytosis by macrophages form foam cells

Question 14

Why does atherosclerosis often occur at branch points

Answer 14

Laminar and turbulent flow

Question 15

Describe laminar flow

Answer 15

Streamlined, outermost layer moves the slowest
Promotes antithrombotic factors, anti-inflammatory factors, NO production and inhibition of SMC proliferation (protective function)
Activates KLF2 and KLF4

Question 16

Describe turbulent flow

Answer 16

Irregular flow
Speed of fluid is continuously undergoing changes in both magnitude and direction
Promotes coagulation, leukocyte adhesion, SMC proliferation, endothelial apoptosis and reduced NO production (damage)
Activates NFKB

Question 17

Describe how epigenetic affects the vascular endothelium

Answer 17

Blood flow will regulate chromatin due to mechanoreceptors recognising changes to blood flow
Stable flow downregulates the expression of DNA methyltransferases which allows the promoter of antiatherogenic genes

Question 18

What is angiogenesis essential for

Answer 18

Hypoxic tissue
Menstrual cycle
Embryonic development
Wound healing

Question 19

Describe angiogenesis

Answer 19

Formation of new vessels by sprouting from pre-existing ones
Promotes plaque growth
Therapeutic angiogenesis prevents damage post-ischaemia

Question 20

What is senescence

Answer 20

Growth arrest that halts proliferation of ageing/damaged cells
Response to stress and damage + cardio risk factors
This causes a distinctive morphology + acquiring of specific markers e.g. b-gal

Question 21

What are the advantages disadvantages of senescence

Answer 21

Advantages:
Prevents transmission of damage to daughter cells
Limited proliferative capacity of human cells in culture

Disadvantages:
Senescent cells are pro-inflammatory and contribute to many diseases

Question 22

Where can senescent endothelial cells be found

Answer 22

Atherosclerotic lesions