Endothelial Dysfunction

Question 1

What are the factors which cause endothelial injury?

Answer 1

Mechanoinjury - shear stress/stretch
Oxidative stress - hypoxia/reoxygenation
Apoptosis and Necrosis - toxin
Inflammation - infectious and non infectious

Question 2

How does shear stress affect endothelial function?

Answer 2

They stimulate several signalling cascades - potassium channel, increase intracellular calcium levels, G protein activation, MAPK signalling and activation of transcription factors

Question 3

How does the endothelium regulate inflammatory responses?

Answer 3

membrane shedding - reduced anticoagulants
increase in procoagulants -vwf thromboxane
increased adhesion molecules
increased permeability
increased TF bearing microparticles
increased leukocyte adhesion and transmigration
can enter due to decrease in barrier function
proinflammatory cytokines are produced

Question 4

How does endothelial dysfunction contribute to pulmonary hypertension?

Answer 4

Reduced NO, pgi2, and increased vasoconstrictors - et1 txa2, increased permability
proliferation that blocks the lume

Question 5

How does the endothelium adapt to shear stress?

Answer 5

They adapt to shear stress by alignment and migration within the direction of flow, when this doesn’t occur there is endothelial damage contributing to the generation of atherosclerotic plaques