Role of protein C in renal dysfunction after polymicrobial sepsis

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 poly...

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Vydáno v:Journal of the American Society of Nephrology Ročník 18; číslo 3; s. 860
Hlavní autoři: Gupta, Akanksha, Berg, David T, Gerlitz, Bruce, Sharma, Ganesh R, Syed, Samreen, Richardson, Mark A, Sandusky, George, Heuer, Josef G, Galbreath, Elizabeth J, Grinnell, Brian W
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States 01.03.2007
Témata:
Acute Kidney Injury - etiology
Acute-Phase Proteins - metabolism
Animals
Apoptosis
Biomarkers - metabolism
Caspase 3 - metabolism
Cecum - surgery
Chemokine CXCL1
Chemokine CXCL2
Chemokines, CXC - metabolism
Disease Models, Animal
Kidney - metabolism
Kidney - pathology
Lipocalins
Nitric Oxide Synthase - metabolism
Protein C - metabolism
Protein C Deficiency - complications
Proto-Oncogene Proteins - metabolism
Rats
Rats, Sprague-Dawley
Sepsis - metabolism
Up-Regulation
ISSN:1046-6673
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Shrnutí: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 polymicrobial sepsis. This study shows that a rapid drop in PC after sepsis is strongly associated with an increase in blood urea nitrogen, renal pathology, and expression of known markers of renal injury, including neutrophil gelatinase-associated lipocalin, CXCL1, and CXCL2. The endothelial PC receptor, which is required for the anti-inflammatory and antiapoptotic activity of activated PC (APC), was significantly increased after cecal ligation and puncture as well as in the microvasculature of human kidneys after injury. Treatment of septic animals with APC reduced blood urea nitrogen, renal pathology, and chemokine expression and dramatically reduced the induction of inducible nitric oxide synthase and caspase-3 activation in the kidney. The data demonstrate a clear link between acquired PC deficiency and renal dysfunction in sepsis and suggest a compensatory upregulation of the signaling receptor. Moreover, these data suggest that APC treatment may be effective in reducing inflammatory and apoptotic insult during sepsis-induced acute renal failure.
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ISSN:1046-6673
DOI:10.1681/ASN.2006101167