Endothelial Function and Exercise Flashcards
What are the three main layers of an artery?
Tunica adventia
Tunica Media
Tunica Intima
What is the structure/components/function of each arterial layer?
Tunica adventia - mainly collagen and elastin - anchoring and structural support
Tunica Media - smooth muscle cells and elastin fibres - vaso constriction/dilation
Tunica Intima - endothelial cells (single layer) attached to basement membrane - sense signals eg hormones, blood flow - can secrete substances to smooth muscles causing contriction of dilation
What is the first stage of atherosclerosis?
- Endothelial dysfunction - characterised by damage to endothelial cells - increased permeability amongst other things (Less NO - problems)
What is the second stage of atherosclerois?
- LDLs invade sub-endothelial space
2. Leukocytes adhere and migrate beneath endothelium (injury to endothelial cells causes an inflammatory response)
What is the third stage atherosclerosis?
- Leucoctyes - differentiate into macrophages and engulf and retain oxidised LDL becoming foam cells
- Foam cells undergo apoptosis and die
- T lympocytes release cytokines which causes smooth muscle cells to migrate from tunica media to the tunica intima
Progression - accumulation of lipid and smooth muscle cells move to top of plaque forming fibrous cap.
What causes damage to endothelium? (6)
- HTN
- ROS
- Turbulent blood flow
- Hyperlipidaemia
- Hyperglycaemia
- Homoctsteinaemia
Endothelial cells produce NO, what are the anti-atherogenic properties of NO? (5)
- Mediates vasodilation (more functional)
- Inhibits leucocyte adhesion and infiltration
- Inhibits platelet adherence and aggregation
- Prevents oxidation modification of LDLs
- Inhibits proliferation of smooth muscle cells
What is the definition of shear stress?
Frictional force of blood flow travelling parallel to endothelial cells.
What is POISEUILLE’S equation?
shear stress =
4 x blood viscosity x blood flow / 4πr3
What does increase in blood flow lead to (simply)?
Increase in shear stress - increase in NO production - increase in arterial wall diamter
Describe how endothelial cells sense change in the lumen?
- Mechanosensors such as the glycocalyx sense the increase in shear stress. Glycocalyx senses this change through displacement of long hair like structures which protrude into the lumen.
- The cytoskeleton of the endothelial cell transduces the signal and leads to activation of the nucleus and PI3k/AKt pathway.
What is the PI3k/AKt pathway?
- PI3k/AKt phosphorylates eNOS, actvating it.
- The activated eNOS converts L-Arginine to NO.
- No diffuses into blood and into smooth muscle cells.
How does NO cause smooth muscle cell relaxation?
NO activates soluble guanylate cyclase.
This causes the dephosphorylation of GTP to cyclic GMP (cGMP) (a secondary messenger. Which induces relaxation by:
- Increased intracellular cGMP, which inhibits calcium entry into the cell, and decreases intracellular calcium concentrations
- Activates K+ channels, which leads to hyperpolarization and relaxation.
- stimulates a cGMP-dependent protein kinase that activates myosin light chain phosphatase, the enzyme that dephosphorylates myosin light chains, which leads to smooth muscle relaxation.
What is uncoupling of eNOS? (3 points)
If reductions in BH4 or L-Arginine can get uncoupling of eNOS. (caused typically by inflammation)
Produces reactive oxide species instead of NO
These can oxidise LDL
NB can supplemet people with these factors but not suitable for long term
How can you measure endothelial function?
FMD - flow medial dilatation
- image using USS and cuff forearm
- Create ischameia in hand (5 mins)
- Remove cuff - reactive hyperaemia - increases sheer stress - increases diameter
- calculate increase size in diameter - eg 11%
