The protein c-thrombomodulin mechanism: regulating multiple biological systems

Published on October 1, 2007 Reviewed on August 12, 2020   45 min

A selection of talks on Cell Biology

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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.

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