The APC–PCI complex concentration predicts outcome of aortic surgery

Nilsson, Gunnar; Strandberg, Karin; Astermark, Jan; Vernersson, E.; Stenflo, Johan; Berntorp, Erik

doi:10.1016/j.thromres.2006.10.004

Cited by 6 publications

(5 citation statements)

References 35 publications

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“…In humans, APC–PCI complex is indicative of atherosclerosis and aortic aneurysms [115], an early indicator of myocardial infarction [116] and predicts poor patient outcome after aortic surgery [117]. Additionally, APC–PCI complex is increased (4‐fold) in patients with FV Leiden who have suffered a previous venous thrombosis [118].…”

Section: Serpins In Hemostasis and Fibrinolysismentioning

confidence: 99%

Serpins in thrombosis, hemostasis and fibrinolysis

Rau

Beaulieu

Huntington

et al. 2007

Journal of Thrombosis and Haemostasis

290

242

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Summary. Hemostasis and fibrinolysis, the biological processes that maintain proper blood flow, are the consequence of a complex series of cascading enzymatic reactions. Serine proteases involved in these processes are regulated by feedback loops, local cofactor molecules, and serine protease inhibitors (serpins). The delicate balance between proteolytic and inhibitory reactions in hemostasis and fibrinolysis, described by the coagulation, protein C and fibrinolytic pathways, can be disrupted, resulting in the pathological conditions of thrombosis or abnormal bleeding. Medicine capitalizes on the importance of serpins, using therapeutics to manipulate the serpin–protease reactions for the treatment and prevention of thrombosis and hemorrhage. Therefore, investigation of serpins, their cofactors, and their structure–function relationships is imperative for the development of state‐of‐the‐art pharmaceuticals for the selective fine‐tuning of hemostasis and fibrinolysis. This review describes key serpins important in the regulation of these pathways: antithrombin, heparin cofactor II, protein Z‐dependent protease inhibitor, α1‐protease inhibitor, protein C inhibitor, α2‐antiplasmin and plasminogen activator inhibitor‐1. We focus on the biological function, the important structural elements, their known non‐hemostatic roles, the pathologies related to deficiencies or dysfunction, and the therapeutic roles of specific serpins.

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Section: Serpins In Hemostasis and Fibrinolysismentioning

confidence: 99%

Serpins in thrombosis, hemostasis and fibrinolysis

Rau

Beaulieu

Huntington

et al. 2007

Journal of Thrombosis and Haemostasis

290

242

View full text Add to dashboard Cite

show abstract

“…In order to define new markers for myocardial or thrombotic diseases, PCI and the PCI-APC complex have been frequent targets of interest. Indeed elevated blood plasma levels of PCI were detected in male survivors of myocardial infarction [5] and high APC-PCI levels are associated with higher early death rates after aortic surgery [6]. Watanabe et al [7] found higher APC-PCI complex levels in patients suffering from disseminated intravascular coagulation, thrombotic thrombocytopenia, acute myocardial infarction, pulmonary embolism, and deep vein thrombosis.…”

Section: Introductionmentioning

confidence: 99%

Protein C Inhibitor (PCI) Binds to Phosphatidylserine Exposing Cells with Implications in the Phagocytosis of Apoptotic Cells and Activated Platelets

et al. 2014

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Protein C Inhibitor (PCI) is a secreted serine protease inhibitor, belonging to the family of serpins. In addition to activated protein C PCI inactivates several other proteases of the coagulation and fibrinolytic systems, suggesting a regulatory role in hemostasis. Glycosaminoglycans and certain negatively charged phospholipids, like phosphatidylserine, bind to PCI and modulate its activity. Phosphatidylerine (PS) is exposed on the surface of apoptotic cells and known as a phagocytosis marker. We hypothesized that PCI might bind to PS exposed on apoptotic cells and thereby influence their removal by phagocytosis. Using Jurkat T-lymphocytes and U937 myeloid cells, we show here that PCI binds to apoptotic cells to a similar extent at the same sites as Annexin V, but in a different manner as compared to live cells (defined spots on ∼10–30% of cells). PCI dose dependently decreased phagocytosis of apoptotic Jurkat cells by U937 macrophages. Moreover, the phagocytosis of PS exposing, activated platelets by human blood derived monocytes declined in the presence of PCI. In U937 cells the expression of PCI as well as the surface binding of PCI increased with time of phorbol ester treatment/macrophage differentiation. The results of this study suggest a role of PCI not only for the function and/or maturation of macrophages, but also as a negative regulator of apoptotic cell and activated platelets removal.

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“…43 A rise in APC-PCI complexes was found to predict outcome of aortic surgery. 44 In contrast, lower levels of APC-PCI complexes were associated with vascular access failure in hemodialysis patients 45 and vascular atherosclerotic changes in patients with type 2 diabetes. 46 In the latter study, a discrepancy between APC-PCI-and thrombin-antithrombin complexes, an established marker for coagulation activation, was observed.…”

Section: Protein C Inhibitor In Hemostasis and Thrombosismentioning

confidence: 96%

Protein C Inhibitor

Meijers

Herwald

2011

Semin Thromb Hemost

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Protein C inhibitor (PCI) is a serine protease inhibitor and was originally identified as an inhibitor of activated protein C (APC). However, PCI is not specific for APC and also inhibits several proteases involved in coagulation, fibrinolysis, cancer, wound healing, and fertility. The biological function of PCI is unknown due to broad enzyme specificity, its wide tissue distribution, and the lack of a suitable animal model. This review highlights the specific roles of PCI in the areas of hemostasis and thrombosis and fertilization, and it also describes the latest information on the fascinating participation of the protein in intracellular processes, phospholipid binding, and killing of bacteria.

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The APC–PCI complex concentration predicts outcome of aortic surgery

Cited by 6 publications

References 35 publications

Serpins in thrombosis, hemostasis and fibrinolysis

Serpins in thrombosis, hemostasis and fibrinolysis

Protein C Inhibitor (PCI) Binds to Phosphatidylserine Exposing Cells with Implications in the Phagocytosis of Apoptotic Cells and Activated Platelets

Protein C Inhibitor

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