Endothelium lecture 7

Question 1

Describe the maturation if blood vessels

Answer 1

1. Endothelial cell tube
2. Capillary- EC tube, pericyte, basement membrane
3. Arterioles and venules- EC tube, internal elastic lamina, smooth muscle cell, basement membrane, external elastic lamina
4. Lymphatics- endothelial cells and valves, initial lymphatic and collecting lymphatics

Question 2

Describe phenotypic heterogeneity

Answer 2

Arteries- ECs aligned in direction of flow, long and narrow cells, continuous endothelium with many tight junctions, no valves, specific markers- Ephrin B2

Veins- continuous endothelium, shorter wider cells not aligned in direction of flow, have valves, specific markers- Ephrin B4

Epigenetic changes are passed on through cell divisoin

Local envirnment cues mustbe maintained

Question 3

Summarise endothelial function

Answer 3

Endothelial cells line all blood and lymphatic vessels

Endotherlium line blood vessles and in contact with the blood. Mesothelium are non-ctick layer of cells around pericardium on serous membranes (pericardium around heart/lungs).

Regulates vascular homeostasis

Acts as both sensor and effector -blood flow regulation -permeability -homeostasis -neutrophil/leukocyte recruitment -hormone trafficking

Can also contribute to angiogeneis

Question 4

Describe endothelial barrier function

Answer 4

Continuous and non-fenestrated endothelium found in arteries, veins and capillaries in the brain, skin and heart- paracellular transport of water and small solutes, transcytosis- passage of larger solutes - caveole smooth membrane invaginations and vesicles

Fenestrated continuous found in the glomerulus- pores have a diaphragm- permits greater transendothelial transport of fluids and solutes

Sinusoidal/discontinous endothelium found in the liver- large fenestrations that lack a diaphragm with a poorly formed basement membrane- high endocytic activity in clathrin-coated pots

Contain tight junctions (claudins, occludins, junctional adhesion molecules- JAMs)

Adherens- VE-cadherin Gap junctions- connexins

Question 5

What are VVOs?

Answer 5

Vesicular-vacuolar organelles

Form transcellular channels when they connect

A major route for transport of fluids and solutes across the endothelium particularly inflammatory situations

Question 6

How does the endothelium provide a non-thrombogenic and anti-coagulent surface

Answer 6

Tissue factor pathway inhibitor- blocks activation of extrinsic pathway

Anti-thrombin III - binds and inactivates thrombin

Thrombomodulin - converts thrombin intoa protein C activator.

Endothelial protein C receptor (EPCR)

Tissue-type plasminogen activator (t-PA)

Prostacyclin and NO - platelet adhesion

Tissue plasminogen activator - activates plasmin = firbrinolysis

ATPase breaks ATP down into AMP so it cannot activate platelets

Question 7

What is the procoagulant by activity of the endothelium?

Answer 7

Induction of tissue factors (F3/thromboplastin)

increased Plasminogen activator inhibitor-1

von Willebrand factor release

Question 8

Describe vascular endothelial growth factor

Answer 8

VEGF (family of growth factrors) is the master regulator of vasculogenesis, physiological and pathological angiogenesis

Selective for endothelial cells via 2 high-affinity receptors

Loss of one allele is embryonic lethal

Over-expression leads to severe abnormalities and death in utero

In the adult VEGF overexpression leads to oedema and tumour growth

Inhibition cause hypertension, proteinuria, bleeding gums

Systemic delivery of VEGF induces increased vascular permeability to fluids nd solultes by indiving VVO transcytosis, fenestrations and loosening of adherins junctions between endothelial cells.

VEGF induces endothelial fenestrae, it promotes actin cytoskeleton rearrrangment and expresssion of diaphragm protein (PV-1). Fenestrae permit transport of hormones into the circulaiton.