Vascular endothelium

Question 1

what are the three layers of the basic structure of blood vessels (not including capillaries and venules)?

Answer 1

tunica adventitia, tunica media, tunica intima

Question 2

what is contained within the tunica adventitia of blood vessels?

Answer 2

vasa vasorum (small blood vessels feeding the blood vessel wall itself) and nerves

Question 3

what is contained within the tunica media of the blood vessels?

Answer 3

smooth muscle cells

Question 4

what is contained within the tunica intima of blood vessels?

Answer 4

endothelium

Question 5

outline the structure of capillaries and venules

Answer 5

formed only by endothelium, supported by some mural cells (pericytes) and a basement membrane

Question 6

what is the function of capillaries

Answer 6

exchanges of nutrients and oxygen between blood and tissues occur

Question 7

Why can damage to the endothelium cause organ dysfunction?

Answer 7

the microvascular endothelium promotes tissue homeostasis

Question 8

what is meant by vascular and endothelial heterogeneity?

Answer 8

Endothelial cells (and pericytes) have organotypic (tissue-specific) properties and unique gene/protein expression profiles

Question 9

what is the importance of endothelial cells lining the vascular system?

Answer 9

acts as a barrier separating blood from tissues, are responsible for regulating blood vessels essential function

Question 10

In vivo, what is the proliferation rate of endothelial cells?

Answer 10

is thought that endothelial cells live a long life and have a low proliferation rate, unless new vessels are required: angiogenesis. However in the gut endothelial cells seem to proliferate

Question 11

What blood vessel functions are controlled by the endothelium?

Answer 11

tissue homeostasis and regeneration, vascular tone, permeability, angiogenesis, inflammation, haemostasis and thrombosis

Question 12

How do endothelial cells maintain tissue homeostasis and regeneration?

Answer 12

contain angiocrine factors

Question 13

what is the most abundant cell in the heart?

Answer 13

endothelial

Question 14

When do endothelial cells have the ability to proliferate and form new vessels? (sprouting angiogenesis)

Answer 14

during wound healing and during cancer

Question 15

how is the angiogenic process regulated?

Answer 15

by a wide array of growth factors and signalling pathways

Question 16

define angiogenesis

Answer 16

is the formation of neo-vessels from pre-existing blood vessels

Question 17

outline the 5 steps of the pathogenesis of atherosclerosis in response to injury

Answer 17

injury results in activation of endothelium.
This causes an increase in endothelial permeability (promotoes leukocyte adhesion).
accumulation of leukocytes in subendothelial space results in foam cell formation.
progresses to formation of advanced lesions of atherosclerosis, more macrophage accumulation forming a necrotic core.
chronic inflammatory lesion which stimulates angiogenesis from vasa vasorum

Question 18

Why and how do tumours become vascular (tumour angiogenesis)

Answer 18

Larger tumours (>1mm3) cannot receive enough oxygen and nutrients purely through diffusion so require a vessel network. the tumour secretes angiogenic factors that stimulate migration, proliferation and neovessel formation by endothelial cells in adjacent established vessels.

Question 19

Outline the steps of the ‘angiogenic switch’ that allows tumours to become vascular

Answer 19

The switch begins with perivascular detachment and vessel dilation, followed by angiogenic sprouting , new vessel formation and maturation, and the recruitment of perivascular cells

Question 20

in tumour angiogenesis, the blood vessel formation will continue as long as _______. and which specific parts of the tumour do the blood vessels feed?

Answer 20

Blood-vessel formation will continue as long as the tumour grows, and the blood vessels specifically feed hypoxic and necrotic areas of the tumour to provide it with essential nutrients and oxygen.

Question 21

describe the structure of tumour blood vessels in comparison to normal blood vessels

Answer 21

irregularly shaped, dilated, tortuous
not organized into definitive venules, arterioles and capillaries
leaky and haemorrhagic, partly due to the overproduction of VEGF
perivascular cells often become loosely associated

Question 22

What do endothelial cells contain that allow them to control angiogenesis?

Answer 22

matrix products such as fibronectin and growth factors such as insulin-like growth factor

Question 23

what do endothelial cells contain that allow them to control inflammation?

Answer 23

adhesion molecules such as ICAM and VCAM, inflammatory mediators such as MHC2 and IL1/6/8

Question 24

what do endothelial cells contain that allow them to control vascular tone and permeability?

Answer 24

vasodilation factors such as NO and vasoconstriction factors such as angiotensin converting enzyme

Question 25

what do endothelial cells contain that allow them to control thrombosis and haemostasis?

Answer 25

antithrombotic factors such as prostacyclin and procoagulant factors such as vWF

Question 26

healthy endothelium has what two characteristics

Answer 26

anti-thrombotic and anti-inflammatory

Question 27

What happens when endothelium loses normal antithrombotic and anti-inflammatory functions? list 2 disorders where this happens

Answer 27

Loss of the normal antithrombotic and anti-inflammatory functions of endothelial cells causes thrombosis with associated inflammation: thromboinflammation. occurs in sepsis and ischamia-reperfusion injury

Question 28

What mechanisms of endothelial dysfunction contribute to the pathogenesis of atherosclerosis?

Answer 28

angiogenesis, shear stress, leuokocyte recruitment and permeability

Question 29

What are the stimuli and risk factors for endothelial cell dysfunction?

Answer 29

Hypercholesterolaemia Diabetes mellitus/metabolic syndrome Hypertension e.g. ANG-II, ROS Sex hormonal imbalance e.g. menopause Ageing Oxidative stress Proinflammatory cytokines e.g. IL-1, TNF Infectious agents e.g. endotoxins Environmental toxins e.g. smoke, pollution Haemodynamic forces e.g. disturbed blood flow

Question 30

how does leukocyte recruitment lead to atherosclerosis?

Answer 30

Leukocytes adhere to activated endothelium of large arteries and get stuck in subendothelial space Monocytes migrate into the subendothelial space, differentiate into macrophages and become foam cells.

Question 31

How does increased vascular permeability lead to atherosclerosis?

Answer 31

Endothelium regulates flux of fluids and molecules from blood to tissues and vice versa Increased permeability results in leakage of plasma proteins through the junctions into the subendothelial space.

Question 32

describe the process of lipid trapping and oxidative modification seen in atherosclerosis caused by increased vascular permeability

Answer 32

Lipoproteins find junctions that are leaky and come through and find proteoglycans Lipoproteins get oxidated in subendothelial space (environment promotes oxidation) Macrophages engulf lipoproteins and form foam cells

Question 33

How does shear stress of endothelium lead to atherosclerosis?

Answer 33

Atherosclerotic plaques occur preferentially at bifurcations and curvatures of the vascular tree because the flow patterns and haemodynamic forces are not uniform in the vascular system.

Question 34

Why do laminar and disturbed flow have different effects on the endothelium?

Answer 34

Laminar blood flow promotes: anti-thrombotic, anti-inflammatory factors endothelial survival Inhibition of SMC proliferation Nitric oxide (NO) production. Disturbed blood flow promotes: Thrombosis, inflammation (leukocyte adhesion) endothelial apoptosis SMC proliferation Loss of Nitric oxide (NO) production

Question 35

What vasodilative molecule is essential for the health of the cardiovascular system?

Answer 35

NO

Question 36

outline the multiple protective effects of nitric oxide on the vascular endothelium

Answer 36

Dilation of blood vessels, reduces oxidation of LDL cholesterol, reduces the release of superoxide chemicals, reduces proliferation of SMC in the vessel wall, inhibit monocyte adhesion, reduces platelet activation

Question 37

What is the JANUS paradox (angiogenesis)?

Answer 37

angiogenesis promotes plaque growth but therapeutic angiogenesis prevents damage post-ischaemia

Question 38

Q1: Which of these statements are correct (1 or more)? A: All blood vessel have the same structure and function B: Angiocrine signals determine the phenotype of the endothelium C: The majority of endothelial cells reside in Arteries D: The majority of endothelial cells reside in Capillaries E: Signals from the microvascular endothelium are required to maintain tissue homeostasis

Answer 38

D: The majority of endothelial cells reside in Capillaries E: Signals from the microvascular endothelium are required to maintain tissue homeostasis

Question 39

Physiologically, in which vessels does leukocyte transmigration occur? A: In large arteries B: In the Aorta C: : In post-capillary Venules

Answer 39

C; in post-capillary venules

Question 40

Which of these processes promotes early development of atherosclerotic plaques (1 or more)? A: Endothelial activation B: Angiogenesis C: Thrombosis D: Permeability E: Leukocyte adhesion

Answer 40

A: endothelial activation D: permeability E: leukocyte adhesion