Vascular Endothelium Flashcards
Where do most endothelial cells reside?
In the microvasculature
Name the 3 layers of blood vessels from innermost to outermost
Tunica intima
Tunica media
Tunica adventitia
What is the tunica intima made of?
Endothelium
What is the tunica media made of?
Smooth muscle cells
What does the tunica adventitia contain?
Vasa vasorum
Do all blood vessels have 3 layers?
No capillaries and venules don’t, they have one layer of endothelium
What supportive cells are present in the basement membrane of capillaries and venules?
Mural cells aka pericytes
What are the factors produced by blood vessels that are needed to maintain tissue homeostasis called?
Angiocrine factors
What are angiocrine factors?
Factors produced by blood vessels that are needed to maintain tissue homeostasis
How thick are endothelial cells?
1-2 micrometres
What is the diameter of an normal endothelial cell?
10-20 micrometers
What is contact inhibition?
When 2 endothelial cells come together and stop growing
How often do endothelial cells proliferate?
Very rarely, they have a long lifespan and will only proliferate when new blood vessels are required
What are some functions controlled by the endothelium of blood vessels?
Tissue homeostasis and regeneration Permeability Vascular tone Inflammation Angiogenesis Haemostasis and thrombosis
What type of cell are endothelial cells?
Heterogeneous
Why is dysfunction of the endothelium so significant?
It contributes to disease more than any other organ, this includes ischaemia, cancer, diabetes etc
What is tissue specific microvasculature?
The idea that not all blood vessels are the same and have adaptations depending on which tissue they supply
What are the characteristics of resting endothelium?
Anti inflammatory
Anti thrombotic
Anti proliferative
What are the characteristics of activated endothelium?
Pro inflammatory
Pro thrombotic
Pro angiogenic
What state must the endothelium be in for atherosclerosis to develop?
It must be chronically activated
What are the 2 main steps in the development of atherosclerosis?
Dysfunction allowing leukocyte migration and adhesion
Formation of a fatty streak due to foam cell activation
Name some stimuli and risk factors for endothelial cell dysfunction
Hypercholesterolaemia Diabetes mellitus Hypertension Sex hormone imbalance Ageing Oxidative stress Proinflammatory cytokines Infectious agents Environmental toxins Haemodynamic forces
What is the leukocyte cascade?
The process by which leukocytes migrate into tissues
What is the leukocyte cascade usually important for?
Fighting inflammation
Describe the process of the leukocyte cascade
Capture Rolling (during which activation occurs) Arrest Adhesion, strengthening and spreading Paracellular and transcellular migration
What type of blood vessel do leukocytes usually adhere to?
The endothelium of post capillary venules
In atherosclerosis what do leukocytes adhere to?
The endothelium of large arteries
Describe how a fatty streak forms in atherosclerosis
Leukocytes adhere to the endothelium of blood vessels
They attempt to migrate into the blood vessel but get stuck in the subendothelial space
Monocytes differentiate into macrophages here and become foam cells
Describe how changes in the permeability of blood vessels affects formation of fatty streaks
As vessels become more permeable, lipoproteins can easily leak through the junctions into the subendothelial space
Here the lipoproteins are oxidised and combine with macrophages to form foam cells
How long does the development of atherosclerosis take?
A long time, the formation of foam cells is not a quick process
Where do atherosclerotic plaques form preferentially?
In curvatures or bifurcations of vessels
Why do atherosclerotic plaques form in specific places preferentially?
Flow patterns and haemodynamic forces are not uniform in the vascular system
Describe blood flow and sheer stress in straight parts of arteries
There is laminar flow
Sheer stress is high and directional
Describe blood flow and sheer stress in the branches and curvatures of arteries
Flow is disturbed
Sheer stress is low
What does laminar flow promote
Anti thrombotic and anti inflammatory factors
Endothelial survival
Inhibition of SMC proliferation
Nitric oxide production
What does disturbed flow promote
Thrombosis, inflammation (leukocyte adhesion)
Endothelial apoptosis
SMC proliferation
Loss of nitric oxide production
What is the significance of nitric oxide in relation to the cardiovascular system?
It is a key regulator of the system, it:
dilates blood vessels
Reduces platelet stickiness
Reduces oxidation of LDL cholesterol (a major component of plaque)
Reduces release of superoxide radicals
reduces multiplication of smooth muscle cells of the artery wall
Reduces monocyte stickiness (prevents the formation of plaque)
What happens to nitric oxide production that encourages development of atherosclerosis?
Reduced production
Define angiogenesis
The formation of new blood vessels via sprouting from existing vessles
What is the main trigger for angiogenesis
Hypoxia
What is the Janus paradox?
The idea that angiogenesis can be both good and bad:
It is bad as it promotes plaque growth
It is good as therapeutic angiogenesis prevents damage post ischemia
What happens to the endothelium in covid?
There is loss of endothelial homeostasis via systemic endothelial oxidation
What cells are a sign of endothelial damage?
Circulating endothelial cells
What are the 2 possible mechanisms of to the endothelium in covid?
A cytokine storm thats secondary to covid
Covid entering endothelial cells and causing direct damage
What process occurs in covid due to loss of normal endothelium?
Thromboinflammation
