Summary: 4.1 Vascular Health - Endothelium | Lydia Afman

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• 1 Endothelium

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• What are endothelial cells (EC) and what are its functions (4)?

  They cover the lumen of all vessels, forming a selectively permeable barrier (endothelium) between blood and vascular tissue. 
  1: selective permeable barrier
  2: regulation of blood pressure and flow: vasoconstriction and -dilatation
  3: modulate trafficking of circulating blood cells: migration of leukocytes
  4: platelet aggregation

• How is NO produced, and where does it act upon?

  In endothelial cells, NOS is activated by an increase in Ca levels, induced by shear forces.
  L-arganine is converted into NO by iNOS/cNOS.
  NO travels to smooth muscle cells, where it increases cGMP production.
  cGMP lowers Ca levels, activates K+ channels -> hyperpolarization and relaxation -> smooth muscle relaxation

• How does prostacyclin (PGI2 activate vasodilatation?

  partly released in response to shear stress, also inhibits VSMC proliferation
  binds and activates Gs-protein coupled receptor
  signals adenylyl cyclase to produce cAMP -> vasodilatation

• What are the 4 steps of leukocyte adhesion? What factors are needed for each step?

  1: initial formation of reversible attachment: rolling. Selectins (P/L/E)
  2: activation of attached cells: activation. Chemokines (IL-8, MCP-1)
  3: development of stronger, shear-resistant attachment: firm adhesion. Integrins (ECAM-1/2, VCAM-1)
  4: transmigration. PECAM-1

• What are the 3 stages of hemostasis (blood clotting)?

  1: vasoconstriction at site of injury
  2: platelet activation, adhesion and aggregation with von Willebrand factor (vWF)
  3: clot formation with fibrin

• What could be the consequence of too high/low platelet numbers?

  Too low: unable to cover wound:bleedings
  Too high: risk of spontaneous aggregation: blood clotting

• What are the 2 characteristics of endothelial dysfunction?

  1: impaired endothelium-dependent vasodilatation
  2: a specific state of 'endothelial activation': pro-inflammatory, proliferative and procoagulatory
  Powerful independent predictor/early marker for cardiovascular diseases

• What is endothelial activation? What is it implicated in?

  A more specific alteration in endothelial function, implicated in pathophysiology: regulated changes in endoothelial phenotype by expression of cell-surface adhesion molecules and other proteins involved in cell–cell interactions.
  It is implicated in inflammatory responses, atherosclerosis and  ischaemia (restricted tissue blood supply) and reperfusion (damage caused when blood supply returns).

• What are the effects of ROS on the endothelium?

  Superoxide can be dismutated by superoxide dismutase (SOD) to hydrogen peroxide (H2O2), which can act as an EDHF or broken down by catalase: O2(-) -> SOD -> H2O2
  Superoxide is capable to scavenge NO to form peroxynitrite: O2(-) + NO -> ONO2(-)
  oxidative stress associated with reduced endothelium-dependent relaxations

• How do inflammatory cytokines cause endothelial dysfunction (4)?

  1: Induce production of adhesion molecules and cytokines by endothelial cells

  2:
  Alter the balance between endogenous vasodilators (NO) and vasoconstrictors (ET-1) > vasoconstriction

  
  3: TNF-α family can directly induce apoptosis of endothelial cells

  4: Stimulate the production of reactive oxygen species