Galley and Webster 2004 Endothelial physiology Flashcards
What kind of functions can endothelial cells exert?
BBB, releasing vasoactive and pro/antiinflammatory factors, Adhesion molecules for leukocytes
How do ECs transport glucose? Where is the protein most highly expressed?
Via Glut1 and 4
Glut1 is most abundant and is highest in the brain
What amino acid is transported, how is it transported, and why is important for vascular function?
What cytokine can impact this?
L-arginine transported by y+ amino acid transporter, which is located in caveolae with eNOS
Substrate for nitric oxide
TNFalpha can stimulate L-arginine transport
What are caveolae? What does it do for example in relation to transport and also vascular function?
Internalizing structures for transcytosis
Transports albumin for example
Also regulates eNOS and Ca2+ influx channels are localized in caveolae too
What are the molecular underpinnings of transport through the ECs?
Caveolae and tight junctions
What are examples of vasoactive molecules from ECs? How does NO cause dilation?
NO, prostacyclin, ET
NO release to SMCs activated guanylyl cyclase to produce cGMP -> activate kinase to inhibit Ca2+ influx and decrease phosphorylation of MLC -> dilate
(but also remember cGMP activates bestrophin chloride current for constriction in vasomotion, but not tonic contraction)
How does NO contribute to attenuating proinflammatory environment in ECs?
NO stabilizes IkB which inhibits NFkB activity for adhesion molecule expression
What does endothelin-1 do and through which receptors on which cells?
ET-1 acts on ETA on SMCs for constriction and ETB on ECs for dilation generally
What types of molecules are involved in host defence by ECs?
Cytokines, adhesion molecules, chemokine
Give examples of adhesion molecules and the differences.
ICAM1/2 and VCAM
ICAM1 and VCAM expression increases during inflammation to allow leukocyte adhesion and subsequent infiltration
What is an example cytokine that ECs release?
IL-1 for antiinflammatory
Are ECs involved in coagulation?
Yes, they express coagulation related and leukocyte adhesion receptors
Eg. Tissue factor pathway inhibitor which inhibits coagulation
What is a critical molecule for angiogenesis? What is the molecule also involved in?
VEGF produced by many different cells including ECs.
But receptors on ECs
VEGF also involved in inflammatory response through releasing adhesion molecules
What is atherosclerosis and how does ECs contribute to it?
Stiffening of arteries due to plaque buildup (fat and cholesterol, and monocyte adhesion) causing constriction
Active monocyte adhesion and infiltration occurs
LDLs and oxidants reduce availability of NO and thus promote inflammatory response
Reduced NO is an early indication of atherosclerosis
How does ET1 contribute to atherosclerosis?
In addition to vasoconstriction, it can promote growth factors and modify extracellular constituents as well as increase cellular adhesion -> atherosclerotic plaque buildup
Blocking ETA receptor can inhibit atherosclerosis
How does EC contribute to inflammation? What cytokins are involved?
Expression of leukocyte adhesion molecules like ICAM1 and VCAM
TLR4 expression to respond to LPS and promote inflammation
Cytokines like TNFalpha, IL-1 causes increased BBB permeability by reducing tight junction proteins and upregulate adhesion molecules
Endothelial denudation can also occur due to LPS
What kind of changes in EC are seen in hyperglycemia and hypertension?
increased eNOS and NO synthesis in hyperglycemia, and also ICAM1 expression for adhesion
elevated ET-1 associated with hypertension
What kind of diseases are endothelial cells involved in?
hyperglycemia, hypertension, metastatic disease, thrombosis, and atherosclerosis
How are ECs involved in cancer?
melanoma cells express VLA4 which binds endothelial VCAMs.
Cancer cells secrete VEGF to promote angiogenesis to facilitate metastasis
