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The Protein C-Thrombomodulin Mechanism
regulating multiple biological systems.
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Almost 2000 years ago, Claudius Galen, the
Greek physician to gladiators and related
to the emperor of Rome, recognized that
blood travels through arteries and veins.
This was the start to a long journey
to understanding vascular disease.
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In spite of hundreds of years of progress
in understanding the vascular system,
diseases, directly or indirectly related
to its dysfunction continue to be common.
In North America and Europe alone,
pulmonary emboli cause over 100,000
deaths per year, heart disease and
strokes in excess of 1 and a half million.
Infections and cancer, both of which
rely on the vasculature to invade and
disseminate, combine to be the major
killers in the world each year,
as well as a key source of morbidity.
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From our current level of knowledge,
it's remarkable to consider that until
only 40 to 50 years ago, the vascular
endothelium was viewed as being inert,
sort of like a pipe,
the purpose being only to carry blood.
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Since that time the vascular endothelium
has literally been brought to life.
Endothelial cells express all kinds
of proteins on their surface,
secrete cytokines and chemokines, transmit
signals into the underlying tissue and
closely interact with bloodborne proteins,
cells and invading organisms.
At its healthiest we view the endothelial
layer as being quiescent.
In this situation, the endothelial
cell surface may be considered smooth,
protecting against blood
clot formation and
accumulation of white blood cells that
may otherwise promote inflammation.
In response to injury, the endothelial
cell surface becomes activated,
the cells become permeable to proteins and
cells.
They become more sticky, so
that leukocytes adhere to their surface so
that they can invade underlying
tissue to fight infection.
They promote platelet activation and
clot formation and attempts
to restrict the wound to prevent bleeding
and ultimately to promote healing.
Since the state of activation of
the endothelium is dynamically changing in
response to a myriad of
stimuli of varying severity,
forces exist to allow the organism
to respond quickly and
at the right place and to an appropriate
extent to fight infections,
inflammatory stimuli or
wounds and to prevent disease.
