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
