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Antithrombin III/SerpinC1 insufficiency exacerbates renal ischemia/reperfusion injury. Kidney Int 2015 Oct;88(4):796-803

Date

06/25/2015

Pubmed ID

26108065

Pubmed Central ID

PMC4589441

DOI

10.1038/ki.2015.176

Scopus ID

2-s2.0-84942983545   50 Citations

Abstract

Antithrombin III, encoded by SerpinC1, is a major anti-coagulation molecule in vivo and has anti-inflammatory effects. We found that patients with low antithrombin III activities presented a higher risk of developing acute kidney injury after cardiac surgery. To study this further, we generated SerpinC1 heterozygous knockout rats and followed the development of acute kidney injury in a model of modest renal ischemia/reperfusion injury. Renal injury, assessed by serum creatinine and renal tubular injury scores after 24 h of reperfusion, was significantly exacerbated in SerpinC1(+/-) rats compared to wild-type littermates. Concomitantly, renal oxidative stress, tubular apoptosis, and macrophage infiltration following this injury were significantly aggravated in SerpinC1(+/-) rats. However, significant thrombosis was not found in the kidneys of any group of rats. Antithrombin III is reported to stimulate the production of prostaglandin I2, a known regulator of renal cortical blood flow, in addition to having anti-inflammatory effects and to protect against renal failure. Prostaglandin F1α, an assayable metabolite of prostaglandin I2, was increased in the kidneys of the wild-type rats at 3 h after reperfusion. The increase of prostaglandin F1α was significantly blunted in SerpinC1(+/-) rats, which preceded increased tubular injury and oxidative stress. Thus, our study found a novel role of SerpinC1 insufficiency in increasing the severity of renal ischemia/reperfusion injury.

Author List

Wang F, Zhang G, Lu Z, Geurts AM, Usa K, Jacob HJ, Cowley AW, Wang N, Liang M

Authors

Aron Geurts PhD Professor in the Physiology department at Medical College of Wisconsin
Mingyu Liang PhD Vice Chair, Center Director, Professor in the Physiology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Acute Kidney Injury
Aged
Animals
Antithrombin III
Antithrombin III Deficiency
Apoptosis
Biomarkers
Cardiac Surgical Procedures
Creatinine
Disease Models, Animal
Female
Gene Knockdown Techniques
Genetic Predisposition to Disease
Heterozygote
Humans
Kidney
Macrophages
Male
Middle Aged
Oxidative Stress
Phenotype
Prostaglandins F
Rats, Transgenic
Reperfusion Injury
Risk Factors
Severity of Illness Index
Signal Transduction
Time Factors