Loss of ACE2 exacerbates murine renal ischemia-reperfusion injury

Ischemia-reperfusion (I/R) is a model of acute kidney injury (AKI) that is characterized by vasoconstriction, oxidative stress, apoptosis and inflammation. Previous studies have shown that activation of the renin-angiotensin system (RAS) may contribute to these processes. Angiotensin converting enzy...

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Bibliographic Details
Published in:PloS one 2013-08, Vol.8 (8), p.e71433-e71433
Main Authors: Fang, Fei, Liu, George Chu, Zhou, Xiaohua, Yang, Stuart, Reich, Heather Naomi, Williams, Vanessa, Hu, Amanda, Pan, Janice, Konvalinka, Ana, Oudit, Gavin Yadram, Scholey, James William, John, Rohan
Format: Article
Language:English
Subjects:
ACE2
Analysis
Angiotensin
Angiotensin converting enzyme
Angiotensin II
Angiotensin II - metabolism
Angiotensin-converting enzyme 2
Angiotensins
Animal models
Animals
Apoptosis
Biology
Chemokine CCL2 - genetics
Chemokine CCL2 - immunology
Chemokine CXCL2 - genetics
Chemokine CXCL2 - immunology
Chemokines
Chronic kidney failure
Cytokines
Departments
Diabetes
Enzymes
Gene Expression
Health care networks
Histology
Infiltration
Inflammation
Inflammation - enzymology
Inflammation - immunology
Inflammation - pathology
Injuries
Interleukin 6
Interleukin-1beta - genetics
Interleukin-1beta - immunology
Interleukin-6 - genetics
Interleukin-6 - immunology
Ischemia
Kidney - enzymology
Kidney - immunology
Kidney - pathology
Kidney diseases
Kinases
Lymphocytes T
Macrophage inflammatory protein
Macrophage inflammatory protein 2
Macrophages
Macrophages - immunology
Macrophages - pathology
Male
Medicine
Metastases
Mice
Mice, Knockout
Monocyte chemoattractant protein
Monocyte chemoattractant protein 1
mRNA
Nephrology
Neutrophil Infiltration
Neutrophils - immunology
Neutrophils - pathology
Oxidative Stress
Peptidyl-Dipeptidase A - genetics
Peptidyl-Dipeptidase A - immunology
Renin
Renin-Angiotensin System - immunology
Reperfusion
Reperfusion Injury - enzymology
Reperfusion Injury - immunology
Reperfusion Injury - pathology
RNA
Science
T cells
T-Lymphocytes - immunology
T-Lymphocytes - pathology
Transplants & implants
Tumor necrosis factor
Tumor Necrosis Factor-alpha - genetics
Tumor Necrosis Factor-alpha - immunology
Tumor necrosis factor-TNF
Tumors
Vasoconstriction
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Summary:Ischemia-reperfusion (I/R) is a model of acute kidney injury (AKI) that is characterized by vasoconstriction, oxidative stress, apoptosis and inflammation. Previous studies have shown that activation of the renin-angiotensin system (RAS) may contribute to these processes. Angiotensin converting enzyme 2 (ACE2) metabolizes angiotensin II (Ang II) to angiotensin-(1-7), and recent studies support a beneficial role for ACE2 in models of chronic kidney disease. However, the role of ACE2 in models of AKI has not been fully elucidated. In order to test the hypothesis that ACE2 plays a protective role in AKI we assessed I/R injury in wild-type (WT) mice and ACE2 knock-out (ACE2 KO) mice. ACE2 KO and WT mice exhibited similar histologic injury scores and measures of kidney function at 48 hours after reperfusion. Loss of ACE2 was associated with increased neutrophil, macrophage, and T cell infiltration in the kidney. mRNA levels for pro-inflammatory cytokines, interleukin-1β, interleukin-6 and tumour necrosis factor-α, as well as chemokines macrophage inflammatory protein 2 and monocyte chemoattractant protein-1, were increased in ACE2 KO mice compared to WT mice. Changes in inflammatory cell infiltrates and cytokine expression were also associated with greater apoptosis and oxidative stress in ACE2 KO mice compared to WT mice. These data demonstrate a protective effect of ACE2 in I/R AKI.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0071433