. Flashcards
(23 cards)
Galen’s open system
Blood is produced in liver
Arteries and veins are distinct
Arteries carrying both blood (derived from venous
blood through invisible interventricular
holes) and pneuma (derived from the
lungs).
Harvey’s closed circularity system
Heart centered
Blood circulates
….. introduced the term
endothelium
Wilhelm HIS
• He recognized the physiological difference between endothelial
and epithelial cells. However, His did not recognize the
participation of ECs in blood vessel formation
Largest endocrine gland
Endothelium
Endothelium imple monolayer structure BUT has many important roles to maintain vascular
homeostasis.
• It regulates:
• Blood flow
• Vascular tone
• Vascular smooth muscle cell proliferation
• Thrombosis, thrombolysis, platelet adherence
• Inflammatory responses
• Haemostasis
• It produces and releases vasoactive, thrombo-regulatory and growth factor substances.
Vascular endothelial cells, like
most cells, release different
types of membrane vesicles,
including ……………….. in response to
cellular activation or
apoptosis.
microparticles (MP) and exosomes
Endothelial microparticles (EMP) (~100
nm to 1 µm in diameter) result from
endothelial plasma membrane blebbing
and carry endothelial proteins such as;
vascular endothelial cadherin, platelet
endothelial cell adhesion molecule-1,
intercellular cell adhesion molecule
(ICAM)-1, endoglin, E-selectin, S-endo
or αv integrin, Endothelial NO synthase
and vascular endothelial growth factor
receptor (VEGF-R2).
cells from different locations in the same person express different
surface antigens and receptors
…….. between
endothelial cells act as a selective
barrier (e.g. blood–brain barrier)
Tight junctions
Endothelium respond to circulating
vasoactive mediators such as
bradykinin and thrombin
VASODILATORS
Nitric oxide
✔ Prostacyclin: vasodilator
synthesized from arachidonic acid by endothelial cells
in response to inflammatory mediators
✔ Endothelial‐derived hyperpolarizing factor
VASOCONSTRICTORS
✔ Endothelin (ET)
✔ Angiotensin-II (A-II)
✔ Thromboxane-A2 (TXA2)
✔ Free radicals
Endothelins
Three members: ET-1, ET-2 and ET-3.
• Regulate vasomotor tone, cellular
proliferation and hormone production.
• ECs produce only ET-1, also syntesized by
vascular smooth muscle cells.
• Production is induced by hypoxia,
ischemia.
• ET-1 binds to specific receptors on smooth
cells→ vasoconstriction.
Prostacyclin (PGI2)
• Synthesis is induced by disturbances in endothelial function or
vascular haemodynamics.
• Released from ECs and acts in a paracrine manner. • Binds to a specific receptor on platelets and vascular smooth
muscle cells to limit vasoconstriction and influence platelet
deposition.
Nitric Oxide (NO)
• NO is the most abundant free-radical in the body
• It is lipophilic and can diffuse rapidly across biological membranes.
• Short lived, usually degraded or reacted within a few seconds
• The natural form is a gas
NO synthesis
L-arginine → L- citrulline
No syntheses
3 isoforms of NOS
1.Inducible NOS (iNOS) and
constitutive ones:
2. endothelial NOS (eNOS)
3. neuronal NOS (nNOS)
• eNOS and nNOS are
regulated
by Ca2+ and calmodulin
Endothelial cells secrete adhesion molecules:
• E-selectin (expressed by endothelial cells),
• P-selectin (expressed by platelets and endothelial cells),
• intercellular adhesion molecule (ICAM)
• vascular cell adhesion molecule (VCAM)
Endothelial cells regulate leucocyte movement
firm cellular adhesion to the endothelial wall
Activation of the leukocytes by
endothelial cell-bound chemokines leads
activation of leukocyte integrins,
another class of adhesion molecules
Endothelial cells maintain anticogulant activity:
• Express heparan suphate- stimulates antithrombin III.
• Express tissue factor pathway inhibitor (TFPI)- prevents t thrombin formation
Thrombomodulin-thrombin interaction activates
protein C-
strong anticoagulant activity.
• Synthesis of protein S, a cofactor for activated protein C.
•Loss of NO bioactivity in the vessel wall causes
an
impairment in endothelium-dependent vasorelaxation
NO deficiency in the vessel wall promotes
• Inflammation
• Oxidation of lipoproteins
• Smooth muscle proliferation
• Accumulation of lipid rich material
• Platelet activation and thrombus formation
Finally results in atherosclerosis
