Cytoprotective signaling by activated protein C requires protease-activated receptor-3 in podocytes.
Blood 119(3):874 (2012)
The cytoprotective effects of activated protein C (aPC) are well established. In contrast, the receptors and signaling mechanism through which aPC conveys cytoprotection in various cell types remain incompletely defined. Thus, within the renal glomeruli, aPC preserves endothelial cells via a pro...
Recombinant activated protein C attenuates coagulopathy and inflammation when administered early in murine pneumococcal pneumonia.
Thrombosis and Haemostasis 106(6):1189 (2011)
Recombinant human activated protein C (APC), which has both anticoagulant and anti-inflammatory properties, improves survival of patients with severe sepsis. This beneficial effect is especially apparent in patients with pneumococcal pneumonia. Earlier treatment with APC in sepsis has been assoc...
Therapeutic recombinant murine activated protein C attenuates pulmonary coagulopathy and improves survival in murine pneumococcal pneumonia.
Journal of Infectious Diseases 202(10):1600 (2010)
Recombinant human activated protein C (APC) improves survival of patients with severe sepsis; this beneficial effect is especially apparent in patients with pneumococcal pneumonia. The aim of this study was to determine the effect of APC treatment initiated after induction of pneumococcal pneumo...
Activated protein C ameliorates coagulopathy but does not influence outcome in lethal H1N1 influenza: a controlled laboratory study.
Critical care (London, England) 14(2):R65 (2010)
Influenza accounts for 5 to 10% of community-acquired pneumonias and is a major cause of mortality. Sterile and bacterial lung injuries are associated with procoagulant and inflammatory derangements in the lungs. Activated protein C (APC) is an anticoagulant with anti-inflammatory properties tha...
Distinct functions of activated protein C differentially attenuate acute kidney injury.
Journal of the American Society of Nephrology 20(2):267 (2009)
Administration of activated protein C (APC) protects from renal dysfunction, but the underlying mechanism is unknown. APC exerts both antithrombotic and cytoprotective properties, the latter via modulation of protease-activated receptor-1 (PAR-1) signaling. We generated APC variants to study the...
W1609 The Anticoagulant Protein C System Is Expressed and Functionally Active in Mucosal Dendritic and Epithelial Cells and Is Down-Regulated in IBD Patients
Gastroenterology 136(5):A (2009)
Treatment of sepsis-induced acquired protein C deficiency reverses Angiotensin-converting enzyme-2 inhibition and decreases pulmonary inflammatory response.
Journal of Pharmacology and Experimental Therap... 325(1):17 (2008)
The protein C (PC) pathway plays an important role in vascular and immune function, and acquired deficiency during sepsis is associated with increased mortality in both animal models and in clinical studies. However, the association of acquired PC deficiency with the pathophysiology of lung inju...
Proteomic analysis of active multiple sclerosis lesions reveals therapeutic targets.
Nature 451(7182):1076 (2008)
Understanding the neuropathology of multiple sclerosis (MS) is essential for improved therapies. Therefore, identification of targets specific to pathological types of MS may have therapeutic benefits. Here we identify, by laser-capture microdissection and proteomics, proteins unique to three ma...
Activated protein C modulates chemokine response and tissue injury in experimental sepsis.
Advances in Experimental Medicine and Biology 614:83 (2008)
The protein C (PC) pathway plays an important role in vascular function, and acquired deficiency during sepsis is associated with increased mortality. We have explored the role of PC suppression in modulating early inflammatory events in a model of polymicrobial sepsis. We show that increased le...
Study of plasma protein C and inflammatory pathways: biomarkers for dimethylnitrosamine-induced liver fibrosis in rats.
European Journal of Pharmacology 575(1-3):158 (2007)
The present investigation was designed to identify potential biomarker(s) and assess the involvement of inflammatory pathway in dimethylnitrosamine (DMN)-induced liver fibrosis in rats. Following DMN-treatment (10 mg/ml/kg, i.p., given three consecutive days each week for 4 weeks) body and liver...
Activated protein C decreases tumor necrosis factor related apoptosis-inducing ligand by an EPCR- independent mechanism involving Egr-1/Erk-1/2 activation.
Arteriosclerosis, Thrombosis, and Vascular Biology 27(12):2634 (2007)
Background- APC is an antithrombotic and antiinflammatory serine protease that plays an important role in vascular function. We report that APC can suppress the proapoptotic mediator TRAIL in human umbilical vein endothelial cells, and we have investigated the signaling mechanism.
APC inhibited ...
Activated protein C protects against diabetic nephropathy by inhibiting endothelial and podocyte apoptosis.
Nature Medicine 13(11):1349 (2007)
Data providing direct evidence for a causative link between endothelial dysfunction, microvascular disease and diabetic end-organ damage are scarce. Here we show that activated protein C (APC) formation, which is regulated by endothelial thrombomodulin, is reduced in diabetic mice and causally l...
Polymeric coatings that mimic the endothelium: combining nitric oxide release with surface-bound active thrombomodulin and heparin.
Biomaterials 28(28):4047 (2007)
Multi-functional bilayer polymeric coatings are prepared with both controlled nitric oxide (NO) release and surface-bound active thrombomodulin (TM) alone or in combination with immobilized heparin. The outer-layer is made of CarboSil, a commercially available copolymer of silicone rubber (SR) a...
Activated protein C suppresses adrenomedullin and ameliorates lipopolysaccharide-induced hypotension.
Shock 28(4):468 (2007)
Activated protein C (APC) is an important modulator of vascular function that has antithrombotic and anti-inflammatory properties. Studies in humans have shown modulation of endotoxin-induced hypotension by recombinant human APC, drotrecogin alfa (activated), however, the mechanism for this effe...
Polymeric coatings that mimic the endothelium: Combining nitric oxide release with surface-bound active thrombomodulin and heparin
Biomaterials 28(28):4047 (2007)
Multi-functional bilayer polymeric coatings are prepared with both controlled nitric oxide (NO) release and surface-bound active thrombomodulin (TM) alone or in combination with immobilized heparin. The outer-layer is made of CarboSil, a commercially available copolymer of silicone rub...
Activated protein C ameliorates LPS-induced acute kidney injury and downregulates renal INOS and angiotensin 2.
American Journal of Physiology - Renal Physiology 293(1):F245 (2007)
Endothelial dysfunction contributes significantly to acute renal failure (ARF) during inflammatory diseases including septic shock. Previous studies have shown that activated protein C (APC) exhibits anti-inflammatory properties and modulates endothelial function. Therefore, we investigated the ...
Crucial role of the protein C pathway in governing microvascular inflammation in inflammatory bowel disease.
Journal of Clinical Investigation 117(7):1951 (2007)
Endothelial protein C receptor (EPCR) and thrombomodulin (TM) are expressed at high levels in the resting microvasculature and convert protein C (PC) into its activated form, which is a potent anticoagulant and antiinflammatory molecule. Here we provide evidence that in Crohn disease (CD) and ul...
Role of protein C in renal dysfunction after polymicrobial sepsis.
Journal of the American Society of Nephrology 18(3):860 (2007)
Protein C (PC) plays an important role in vascular function, and acquired deficiency during sepsis is associated with increased mortality in both animal models and in clinical studies. This study explored the consequences of PC suppression on the kidney in a cecal ligation and puncture model of ...
FoxA2 involvement in suppression of protein C, an outcome predictor in experimental sepsis.
Clinical and Vaccine Immunology 13(3):426 (2006)
Low levels of protein C (PC) predict outcome as early as 10 h after insult in a rat polymicrobial sepsis model and were associated with suppression of PC mRNA, upstream transcription factor FoxA2, and cofactor hepatocyte nuclear factor 6 (HNF6). Small interfering RNA suppression of FoxA2 in isol...
Evaluation of protein C and other biomarkers as predictors of mortality in a rat cecal ligation and puncture model of sepsis.
Critical Care Medicine 32(7):1570 (2004)
To evaluate protein C and other factors associated with the septic response as predictors of mortality in a clinically relevant animal model of sepsis.
Eli Lilly and Company discovery research laboratory.
Forty female Sprague Dawley rats weighing 245-265 g.