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Recent advances in disseminated intravascular coagulation: endothelial cells and fibrinolysis in sepsis-induced DIC.

Madoiwa S - J Intensive Care (2015)

Bottom Line: Endothelial cell dysfunction is one of the early signs of systemic inflammation, and it is a trigger of multiple organ failure in sepsis.The marked increase in plasminogen activator inhibitor-1 level causes fibrinolytic shutdown in endotoxemia or sepsis and is one of the most important predictors of multiple organ dysfunction during sepsis-induced disseminated intravascular coagulation (DIC).Leukocytes exhibit the first-line response to microorganisms.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Laboratory Medicine, Tokyo Saiseikai Central Hospital, 1-14-17, Mita, Minato-ku, Tokyo 108-0073 Japan ; Department of Clinical Laboratory Medicine, Jichi Medical University, 3311-1, Yakushi-ji, Shimotsuke, Tochigi 329-0498 Japan.

ABSTRACT
Endothelial cells are highly active, sensing and responding to signals from extracellular environments. They act as gatekeepers, mediating the recruitment and extravasation of proinflammatory leukocytes to the sites of tissue damage or infection. Endothelial cells participate in fibrinolysis by secreting tissue-type plasminogen activator, which converts plasminogen to active enzyme plasmin through constitutive and regulated pathways. Fibrinolysis systems and inflammation are tightly linked, as both responses are major host defense systems against both healing processes of tissue repair as well as pathogenic microorganisms. Endothelial cell dysfunction is one of the early signs of systemic inflammation, and it is a trigger of multiple organ failure in sepsis. The marked increase in plasminogen activator inhibitor-1 level causes fibrinolytic shutdown in endotoxemia or sepsis and is one of the most important predictors of multiple organ dysfunction during sepsis-induced disseminated intravascular coagulation (DIC). Leukocytes exhibit the first-line response to microorganisms. Leukocyte-derived elastase degrades cross-linked fibrin to yield molecular species distinct from those generated by plasmin. The alternative systems for fibrinolysis that interact with the plasminogen activator-plasmin systems may play crucial roles in the lysis of fibrin clots in sepsis-induced DIC.

No MeSH data available.


Related in: MedlinePlus

Schematic representation of endothelial functions in physiological states. FVIIa, activated factor VII; FVi, inactivated factor V; TF, tissue factor; AT-III, antithrombin-III; TFPI, tissue factor pathway inhibitor; PC, protein C; APC, activated protein C; PS, protein S; TM, thrombomodulin; EPCR, endothelial protein C receptor; NO, nitrate oxide; PGI2, prostaglandin I2.
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Fig1: Schematic representation of endothelial functions in physiological states. FVIIa, activated factor VII; FVi, inactivated factor V; TF, tissue factor; AT-III, antithrombin-III; TFPI, tissue factor pathway inhibitor; PC, protein C; APC, activated protein C; PS, protein S; TM, thrombomodulin; EPCR, endothelial protein C receptor; NO, nitrate oxide; PGI2, prostaglandin I2.

Mentions: Endothelial cells form the inner lining of the vascular endothelium and act as a selective barrier, controlling the trans-cellular exchange of fluids, ions, and bioactive molecules between circulating blood and perivascular tissues [4]. Under typical physiological conditions, endothelial cells actively sense and respond to signals around from their extracellular environments. Endothelial cells regulate hemostatic balance by site-specific release of procoagulants and anticoagulation factors. Endothelial cells synthesize von Willebrand factor (VWF) and protease-activated receptors (PARs) for hemostasis. They also express many molecules involved in the control of platelet function, and blood coagulation systems, including prostacyclin, nitric oxide, tissue factor pathway inhibitor, heparin sulfate, thrombomodulin, and endothelial protein C receptor (EPCR) (Figure 1) [5]. In particular, thrombomodulin-mediated binding to thrombin efficiently converts protein C to activated protein C, which results in limited inactivation of coagulation factors Va and VIIIa by proteolysis, in the presence of cofactor protein S [6]. The generation of activated protein C is accelerated by binding to EPCR and by presentation to the thrombin-thrombomodulin complex. The thrombin-thrombomodulin complex plays an indirect role in the suppression of fibrinolysis through the activation of an inhibitor, thrombin activatable fibrinolysis inhibitor (TAFI) [7]. Endothelial cells participate in fibrinolysis by secreting tissue-type plasminogen activator (tPA), which converts plasminogen to active enzyme plasmin through constitutive and regulated pathways [8,9]. This reaction is controlled by plasminogen receptors including α-enolase, histone H2B, plasminogen receptor, and annexin A2/S100A10 at the surface of endothelial cells [10,11]. The annexin A2 anchors S100A10 on the surface of endothelial cells, which recruits tPA and plasminogen to the carboxyl-terminal lysine residues of the receptor, resulting in enhanced activation of plasminogen by tPA to generate fibrinolytic activity [12]. Ectopic expression and overexpression of annexin A2 lead to uncontrolled production of plasmin, which causes fatal hemorrhagic diatheses due to hyperfibrinogenolysis in patients with malignancy [13,14].Figure 1


Recent advances in disseminated intravascular coagulation: endothelial cells and fibrinolysis in sepsis-induced DIC.

Madoiwa S - J Intensive Care (2015)

Schematic representation of endothelial functions in physiological states. FVIIa, activated factor VII; FVi, inactivated factor V; TF, tissue factor; AT-III, antithrombin-III; TFPI, tissue factor pathway inhibitor; PC, protein C; APC, activated protein C; PS, protein S; TM, thrombomodulin; EPCR, endothelial protein C receptor; NO, nitrate oxide; PGI2, prostaglandin I2.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4940964&req=5

Fig1: Schematic representation of endothelial functions in physiological states. FVIIa, activated factor VII; FVi, inactivated factor V; TF, tissue factor; AT-III, antithrombin-III; TFPI, tissue factor pathway inhibitor; PC, protein C; APC, activated protein C; PS, protein S; TM, thrombomodulin; EPCR, endothelial protein C receptor; NO, nitrate oxide; PGI2, prostaglandin I2.
Mentions: Endothelial cells form the inner lining of the vascular endothelium and act as a selective barrier, controlling the trans-cellular exchange of fluids, ions, and bioactive molecules between circulating blood and perivascular tissues [4]. Under typical physiological conditions, endothelial cells actively sense and respond to signals around from their extracellular environments. Endothelial cells regulate hemostatic balance by site-specific release of procoagulants and anticoagulation factors. Endothelial cells synthesize von Willebrand factor (VWF) and protease-activated receptors (PARs) for hemostasis. They also express many molecules involved in the control of platelet function, and blood coagulation systems, including prostacyclin, nitric oxide, tissue factor pathway inhibitor, heparin sulfate, thrombomodulin, and endothelial protein C receptor (EPCR) (Figure 1) [5]. In particular, thrombomodulin-mediated binding to thrombin efficiently converts protein C to activated protein C, which results in limited inactivation of coagulation factors Va and VIIIa by proteolysis, in the presence of cofactor protein S [6]. The generation of activated protein C is accelerated by binding to EPCR and by presentation to the thrombin-thrombomodulin complex. The thrombin-thrombomodulin complex plays an indirect role in the suppression of fibrinolysis through the activation of an inhibitor, thrombin activatable fibrinolysis inhibitor (TAFI) [7]. Endothelial cells participate in fibrinolysis by secreting tissue-type plasminogen activator (tPA), which converts plasminogen to active enzyme plasmin through constitutive and regulated pathways [8,9]. This reaction is controlled by plasminogen receptors including α-enolase, histone H2B, plasminogen receptor, and annexin A2/S100A10 at the surface of endothelial cells [10,11]. The annexin A2 anchors S100A10 on the surface of endothelial cells, which recruits tPA and plasminogen to the carboxyl-terminal lysine residues of the receptor, resulting in enhanced activation of plasminogen by tPA to generate fibrinolytic activity [12]. Ectopic expression and overexpression of annexin A2 lead to uncontrolled production of plasmin, which causes fatal hemorrhagic diatheses due to hyperfibrinogenolysis in patients with malignancy [13,14].Figure 1

Bottom Line: Endothelial cell dysfunction is one of the early signs of systemic inflammation, and it is a trigger of multiple organ failure in sepsis.The marked increase in plasminogen activator inhibitor-1 level causes fibrinolytic shutdown in endotoxemia or sepsis and is one of the most important predictors of multiple organ dysfunction during sepsis-induced disseminated intravascular coagulation (DIC).Leukocytes exhibit the first-line response to microorganisms.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Laboratory Medicine, Tokyo Saiseikai Central Hospital, 1-14-17, Mita, Minato-ku, Tokyo 108-0073 Japan ; Department of Clinical Laboratory Medicine, Jichi Medical University, 3311-1, Yakushi-ji, Shimotsuke, Tochigi 329-0498 Japan.

ABSTRACT
Endothelial cells are highly active, sensing and responding to signals from extracellular environments. They act as gatekeepers, mediating the recruitment and extravasation of proinflammatory leukocytes to the sites of tissue damage or infection. Endothelial cells participate in fibrinolysis by secreting tissue-type plasminogen activator, which converts plasminogen to active enzyme plasmin through constitutive and regulated pathways. Fibrinolysis systems and inflammation are tightly linked, as both responses are major host defense systems against both healing processes of tissue repair as well as pathogenic microorganisms. Endothelial cell dysfunction is one of the early signs of systemic inflammation, and it is a trigger of multiple organ failure in sepsis. The marked increase in plasminogen activator inhibitor-1 level causes fibrinolytic shutdown in endotoxemia or sepsis and is one of the most important predictors of multiple organ dysfunction during sepsis-induced disseminated intravascular coagulation (DIC). Leukocytes exhibit the first-line response to microorganisms. Leukocyte-derived elastase degrades cross-linked fibrin to yield molecular species distinct from those generated by plasmin. The alternative systems for fibrinolysis that interact with the plasminogen activator-plasmin systems may play crucial roles in the lysis of fibrin clots in sepsis-induced DIC.

No MeSH data available.


Related in: MedlinePlus