Levels of protein C and soluble thrombomodulin in critically ill patients with acute kidney injury: a multicenter prospective observational study.
PLoS ONE 10(3):e0120770 (2015)
Endothelial dysfunction contributes to the development of acute kidney injury (AKI) in animal models of ischemia reperfusion injury and sepsis. There are limited data on markers of endothelial dysfunction in human AKI. We hypothesized that Protein C (PC) and soluble thrombomodulin (sTM) levels c...
Soluble thrombomodulin reduces inflammation and prevents microalbuminuria induced by chronic endothelial activation in transgenic mice.
American Journal of Physiology: Renal, Fluid & ... 302(6):F703 (2012)
Chronic kidney disease pathogenesis involves both tubular and vascular injuries. Despite abundant investigations to identify the risk factors, the involvement of chronic endothelial dysfunction in developing nephropathies is insufficiently explored. Previously, soluble thrombomodulin (sTM), a co...
Soluble thrombomodulin protects ischemic kidneys.
Journal of the American Society of Nephrology 20(3):524 (2009)
Altered coagulation and inflammation contribute to the pathogenesis of ischemic renal injury. Thrombomodulin is a necessary factor in the anticoagulant protein C pathway and has inherent anti-inflammatory properties. We studied the effect of soluble thrombomodulin (sTM) in a hypoperfusion model ...
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...
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...
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...
Negative regulation of inducible nitric-oxide synthase expression mediated through transforming growth factor-beta-dependent modulation of transcription factor TCF11.
Journal of Biological Chemistry 282(51):36837 (2007)
Inducible nitric-oxide synthase (iNOS) plays a central role in the regulation of vascular function and response to injury. A central mediator controlling iNOS expression is transforming growth factor-beta (TGF-beta), which represses its expression through a mechanism that is poorly understood. W...
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...
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...
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 ...
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...
NF-(kappa)B mediates amyloid beta peptide-stimulated activity of the human apolipoprotein E gene promoter in human astroglial cells.
Molecular Brain Research 136(1-2):177 (2005)
The apolipoprotein E gene (APOE) plays an important role in the pathogenesis of Alzheimer's disease (AD), and amyloid plaque comprised mostly of the amyloid-beta peptide (A(beta)) is one of the major hallmarks of AD. However, the relationship between these two important molecules is poorly under...
Smad6s regulates plasminogen activator inhibitor-1 through a protein kinase C-beta-dependent up-regulation of transforming growth factor-beta.
Journal of Biological Chemistry 280(15):14943 (2005)
Plasminogen activator inhibitor-1 (PAI-1) is a serpin class protease inhibitor that plays a central role in the regulation of vascular function and tissue remodeling by modulating thrombosis, inflammation, and the extracellular matrix. A central mediator controlling PAI-1 is transforming growth ...
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.
Engineering the proteolytic specificity of activated protein C improves its pharmacological properties.
PNAS 100(8):4423 (2003)
Human activated protein C (APC) is an antithrombotic, antiinflammatory serine protease that plays a central role in vascular homeostasis, and activated recombinant protein C, drotrecogin alfa (activated), has been shown to reduce mortality in patients with severe sepsis. Similar to other serine ...
Modulation of thrombomodulin-dependent activation of human protein C through differential expression of endothelial Smads.
Journal of Biological Chemistry 277(51):49815 (2002)
Protein C is a plasma protease that in its active form plays a central role in the regulation of vascular function by modulating thrombosis, inflammation, and apoptosis. A central player in this pathway is the cytokine-regulated receptor thrombomodulin (TM), which functions as a co-factor for th...