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The normal role of Activated Protein C in maintaining homeostasis and its relevance to critical illness.

Esmon CT - Crit Care (2001)

Bottom Line: Thrombin is a multifunctional protein, with procoagulant, inflammatory and anticoagulant effects.When the level of thrombomodulin or Protein C is reduced in sepsis there is a vicious cycle of coagulation and inflammation, with potentially lethal consequences.In vitro studies and animal models have shown that Activated Protein C blunts the inflammatory and coagulant response to sepsis through a variety of mechanisms.

View Article: PubMed Central - PubMed

Affiliation: Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Howard Hughes Medical Institute, Oklahoma City 73104, USA. Charles-Esmon@omrf.ouhsc.edu

ABSTRACT
Thrombin is a multifunctional protein, with procoagulant, inflammatory and anticoagulant effects. Binding of thrombin to thrombomodulin results in activation of Protein C and initiation of the Activated Protein C anticoagulant pathway, a process that is augmented by the endothelial cell Protein C receptor (EPCR). Activated Protein C has demonstrated antithrombotic, anti-inflammatory, and profibrinolytic properties. Its antithrombotic activity is particularly important in the microcirculation, and Protein C deficiency is associated with microvascular thrombosis. Activated Protein C has also been shown to modulate inflammation. When the level of thrombomodulin or Protein C is reduced in sepsis there is a vicious cycle of coagulation and inflammation, with potentially lethal consequences. In vitro studies and animal models have shown that Activated Protein C blunts the inflammatory and coagulant response to sepsis through a variety of mechanisms.

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Activated Protein C/EPCR-mediated anticoagulant pathway. APC, Activated Protein C; MP, metalloproteinase; Palm, palmitate; PC, Protein C; PMA, phorbol myristate acetate; TM, thrombomodulin; RRC, Arg,Arg,Lys. Adapted from Esmon [18].
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Figure 8: Activated Protein C/EPCR-mediated anticoagulant pathway. APC, Activated Protein C; MP, metalloproteinase; Palm, palmitate; PC, Protein C; PMA, phorbol myristate acetate; TM, thrombomodulin; RRC, Arg,Arg,Lys. Adapted from Esmon [18].

Mentions: The Activated Protein C/EPCR-mediated anticoagulant pathway is illustrated in Fig. 8 [18]. The EPCR is synthesized on the endothelial cell surface and moves to specialized regions (caveolae) in the endothelium, through which it is able to enter the cell and then the cell nucleus. Once inside the nucleus, it is able to redirect the gene expression profiles within the cell. Unlike other plasma membrane receptors, EPCR is also capable of carrying Activated Protein C into the nucleus, with subsequent alterations to some of the gene products.


The normal role of Activated Protein C in maintaining homeostasis and its relevance to critical illness.

Esmon CT - Crit Care (2001)

Activated Protein C/EPCR-mediated anticoagulant pathway. APC, Activated Protein C; MP, metalloproteinase; Palm, palmitate; PC, Protein C; PMA, phorbol myristate acetate; TM, thrombomodulin; RRC, Arg,Arg,Lys. Adapted from Esmon [18].
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3300084&req=5

Figure 8: Activated Protein C/EPCR-mediated anticoagulant pathway. APC, Activated Protein C; MP, metalloproteinase; Palm, palmitate; PC, Protein C; PMA, phorbol myristate acetate; TM, thrombomodulin; RRC, Arg,Arg,Lys. Adapted from Esmon [18].
Mentions: The Activated Protein C/EPCR-mediated anticoagulant pathway is illustrated in Fig. 8 [18]. The EPCR is synthesized on the endothelial cell surface and moves to specialized regions (caveolae) in the endothelium, through which it is able to enter the cell and then the cell nucleus. Once inside the nucleus, it is able to redirect the gene expression profiles within the cell. Unlike other plasma membrane receptors, EPCR is also capable of carrying Activated Protein C into the nucleus, with subsequent alterations to some of the gene products.

Bottom Line: Thrombin is a multifunctional protein, with procoagulant, inflammatory and anticoagulant effects.When the level of thrombomodulin or Protein C is reduced in sepsis there is a vicious cycle of coagulation and inflammation, with potentially lethal consequences.In vitro studies and animal models have shown that Activated Protein C blunts the inflammatory and coagulant response to sepsis through a variety of mechanisms.

View Article: PubMed Central - PubMed

Affiliation: Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Howard Hughes Medical Institute, Oklahoma City 73104, USA. Charles-Esmon@omrf.ouhsc.edu

ABSTRACT
Thrombin is a multifunctional protein, with procoagulant, inflammatory and anticoagulant effects. Binding of thrombin to thrombomodulin results in activation of Protein C and initiation of the Activated Protein C anticoagulant pathway, a process that is augmented by the endothelial cell Protein C receptor (EPCR). Activated Protein C has demonstrated antithrombotic, anti-inflammatory, and profibrinolytic properties. Its antithrombotic activity is particularly important in the microcirculation, and Protein C deficiency is associated with microvascular thrombosis. Activated Protein C has also been shown to modulate inflammation. When the level of thrombomodulin or Protein C is reduced in sepsis there is a vicious cycle of coagulation and inflammation, with potentially lethal consequences. In vitro studies and animal models have shown that Activated Protein C blunts the inflammatory and coagulant response to sepsis through a variety of mechanisms.

Show MeSH
Related in: MedlinePlus