Vascular Endothelium Flashcards
Where do 98% of endothelial cells reside?
Within the microvasculature
What are the three layers of blood vessels?
- Tunica adventitia
- Tunica media
- Tunica intima
(Except for capillaries and venules)
What does the tunica adventitia include?
- Vasa vasorum
- Nerves
What does the tunica media include?
Smooth muscle cells
Whartdoes the tunica intima include?
Endothelium
How are capillaries and venules formed?
- Only by endothelium
- Supported by some mural cells (pericytes)
- A basement membrane
What happens at capillaries?
exchanges of nutrients and oxygen between blood and tissues
What does the microvascular endothelium promote?
tissue homeostasis
What can damage to the endothelium cause?
Organ dysfunction
What is the microvascular endothelium a source of?
angiocrine factors
What are angiocrine factors for the maintenance of?
- tissue homeostasis
- organ regeneration
What does a dysfunctional endothelium contribute to?
Disease more than any other organ e.g. •Ischemia •Chronic inflammatory diseases •Cancer •Diabetes -Atherosceleoris
What are examples of organs with tissue-specific microvasculature?
- Heart
- Lung
- Liver
- Kidney
- Brain
What do endothelial cells and microvasculature have?
organotypic (tissue specific) properties and expression profiles
What is the barrier that the endothelium creates?
separates blood from tissues
What is the surface area of endothelial cells?
> 1000 m2
What is the weight of endothelial cells?
weight >100 g
What are endothelial cells like?
- very flat
- about 1-2 µm thick
- 10-20 µm in diameter
How are the endothelial cells lining the vascular system formed?
by a monolayer of endothelial cells, one cell deep (contact inhibition)
Why is contact inhibition unique?
only epithelial and endothelial cells that do this (2D)
What is contact inhibition?
Process when the junction of two cells come together and form junctions and tell each cells to stop growing
What happens to endothelial cells in vivo?
- live a long life
- low proliferation rate (unless new vessels are required: angiogenesis)
What sort of functions does the endothelium control of blood vessels and tissues?
- Vascular tone
- Angiogenesis
- Permeability
- Inflammation
- Homeostasis and thrombosis
What does it mean that endothelial cells are heterogenous?
their function and phenotype depends on their location
How do endothelial cells affect inflammation?
- Adhestion molecules
- Inflammatory mediators
What are examples of some adhesion molecules?
- ICAMs
- VCAM
- Selectins
What are examples of some inflammatory mediators?
- Interleukins 1, 6, 8
- Leukontrienes
- MHC II
How do endothelial cells affect vascular permeability and tone?
- Vasodilator factors
- Vasoconstricting factors
What are examples of vasodilator factors?
- Nitric oxide
2. Prostacyclin
What are examples of vasoconstricting factors?
- ACE
- Thromboxane A2
- Leukotrienes
- Free radicals
- Endothelin
How does endothelial cells affect angiogenesis?
- growth factors
- matrix products
What are examples of growth factors?
- Insulin like growth factor
- Transforming growth factor
- Colony stimulating factor
How do endothelial cells affect thrombosis and haemostasis?
- Procoagulant factors
- Anti-thrombotic factors
What are examples of antithrombotic factors?
- Prostacyclin
- Thrombomodulin
- Antithrombin
- Plasminogen activator
- Heparin
What are examples of procoagulant factors?
- Von willebrand factor
- Thromboxane A2
- Thromboplastin
- Factor V
- platelet activating factor
- Plasminogen activator inhibitor
What are examples of matrix factors?
- fibronectin
- laminin
- collagen
- proteoglycans
- proteases
What pathways are switches on in resting endothelium?
anti-pathways
What are the pathways?
- Anti-inflammatory
- Anti-thrombotic
- Anti-proliferative
What happens when the endothelium is activated?
Balance switches to pro-pathways
What are the pro-pathways?
- Pro-inflammatory
- Pro-thrombotic
- Pro-angiogenic
What are some risk factors for atherolecelrosis that lead to chronic activation of the endothelium?
- Mechanical stress
- Viruses
- Smoking
- Inflammation
- High blood pressure
- OxLDL
- High glucose
What does chronic activation of the endothelium lead to?
- Thrombosis
- Senescence
- Leukocytes recruitment
- Permeability
LEADS to atherosclerosis
What is the first step in pathogenesis of atherosceleorsis?
- Initial injury caused by risk factors results in activation of endothelium
- Causes an increase in endothelial permeability, increase in the regulation of the systems that promote adhesion of leukocytes
- which should not stick and just flow
What happens to these leukocytes in the pathogenesis of atheroscelerosis?
Leukocytes that adhere tend to migrate into sub-endothelial space
What does this accumulation of leukocytes result in in pathogenesis of atheroscelerosis?
- accumulation of leukocytes into the sub endothelial space
2 phagocytosis of the lipids there results in foam cell formation - process slowly evolves towards formation of advanced complicated lesion of atheroscelerosis
What does this advanced complicated lesion of atheroscelerosis lead to in the pathogenesis of atherosceleoris?
- more and more macrophage accumulate
- therefore necrotic core is formed
- becomes a chronic inflammatory lesion
- even stimulates the formation of angiogenesis from the vast vasorum in the tissue
What is some stimuli of endothelial cell dysfunction in atherogenesis?
- Hypercholesterolaemia
- Diabetes mellitus/metabloic syndrome
- Hypertension
- Sex hormone imbalance
- Ageing
- Oxidative stress
- Pro-inflmmatory cytokines
- Infectious agents
- Environmental toxins
- Haemodyanmic forces
What is an example of hypercholesterolaemia?
oxidatively modified lipoproteins
What is an example of hypertension?
ANG-II and ROS
What is an example of sex hormone imbalance?
oestrogen deficiency and menopause
What are examples of pro-inflammatory cytokines?
IL-1 and TNF
What is an example of infectious agents?
- Bacterial endotoxins
- Viruses
What are examples of environmental toxins?
- Cigarette smoke
- Air pollutants
What is an example of haemodynamic forces?
disturbed blood flow
