Vascular endothelium Flashcards
what are the three layers of the basic structure of blood vessels (not including capillaries and venules)?
tunica adventitia, tunica media, tunica intima
what is contained within the tunica adventitia of blood vessels?
vasa vasorum (small blood vessels feeding the blood vessel wall itself) and nerves
what is contained within the tunica media of the blood vessels?
smooth muscle cells
what is contained within the tunica intima of blood vessels?
endothelium
outline the structure of capillaries and venules
formed only by endothelium, supported by some mural cells (pericytes) and a basement membrane
what is the function of capillaries
exchanges of nutrients and oxygen between blood and tissues occur
Why can damage to the endothelium cause organ dysfunction?
the microvascular endothelium promotes tissue homeostasis
what is meant by vascular and endothelial heterogeneity?
Endothelial cells (and pericytes) have organotypic (tissue-specific) properties and unique gene/protein expression profiles
what is the importance of endothelial cells lining the vascular system?
acts as a barrier separating blood from tissues, are responsible for regulating blood vessels essential function
In vivo, what is the proliferation rate of endothelial cells?
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
What blood vessel functions are controlled by the endothelium?
tissue homeostasis and regeneration, vascular tone, permeability, angiogenesis, inflammation, haemostasis and thrombosis
How do endothelial cells maintain tissue homeostasis and regeneration?
contain angiocrine factors
what is the most abundant cell in the heart?
endothelial
When do endothelial cells have the ability to proliferate and form new vessels? (sprouting angiogenesis)
during wound healing and during cancer
how is the angiogenic process regulated?
by a wide array of growth factors and signalling pathways
define angiogenesis
is the formation of neo-vessels from pre-existing blood vessels
outline the 5 steps of the pathogenesis of atherosclerosis in response to injury
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
Why and how do tumours become vascular (tumour angiogenesis)
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.
Outline the steps of the ‘angiogenic switch’ that allows tumours to become vascular
The switch begins with perivascular detachment and vessel dilation, followed by angiogenic sprouting , new vessel formation and maturation, and the recruitment of perivascular cells
in tumour angiogenesis, the blood vessel formation will continue as long as _______. and which specific parts of the tumour do the blood vessels feed?
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.
describe the structure of tumour blood vessels in comparison to normal blood vessels
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
What do endothelial cells contain that allow them to control angiogenesis?
matrix products such as fibronectin and growth factors such as insulin-like growth factor
what do endothelial cells contain that allow them to control inflammation?
adhesion molecules such as ICAM and VCAM, inflammatory mediators such as MHC2 and IL1/6/8
what do endothelial cells contain that allow them to control vascular tone and permeability?
vasodilation factors such as NO and vasoconstriction factors such as angiotensin converting enzyme
what do endothelial cells contain that allow them to control thrombosis and haemostasis?
antithrombotic factors such as prostacyclin and procoagulant factors such as vWF
healthy endothelium has what two characteristics
anti-thrombotic and anti-inflammatory
What happens when endothelium loses normal antithrombotic and anti-inflammatory functions?
list 2 disorders where this happens
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
What mechanisms of endothelial dysfunction contribute to the pathogenesis of atherosclerosis?
angiogenesis, shear stress, leuokocyte recruitment and permeability
What are the stimuli and risk factors for endothelial cell dysfunction?
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
how does leukocyte recruitment lead to atherosclerosis?
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.
How does increased vascular permeability lead to atherosclerosis?
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.
describe the process of lipid trapping and oxidative modification seen in atherosclerosis caused by increased vascular permeability
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
How does shear stress of endothelium lead to atherosclerosis?
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.
Why do laminar and disturbed flow have different effects on the endothelium?
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
What vasodilative molecule is essential for the health of the cardiovascular system?
NO
outline the multiple protective effects of nitric oxide on the vascular endothelium
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
What is the JANUS paradox (angiogenesis)?
angiogenesis promotes plaque growth but therapeutic angiogenesis prevents damage post-ischaemia
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
D: The majority of endothelial cells reside in Capillaries
E: Signals from the microvascular endothelium are required to maintain tissue homeostasis
Physiologically, in which vessels does leukocyte transmigration occur?
A: In large arteries
B: In the Aorta
C: : In post-capillary Venules
C; in post-capillary venules
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
A: endothelial activation
D: permeability
E: leukocyte adhesion
