Metabolomics assessment reveals oxidative stress and altered energy production in the heart after ischemic acute kidney injury in mice

Acute kidney injury (AKI) is a systemic disease associated with widespread effects on distant organs, including the heart. Normal cardiac function is dependent on constant ATP generation, and the preferred method of energy production is via oxidative phosphorylation. Following direct ischemic cardia...

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Vydáno v:	Kidney international Ročník 95; číslo 3; s. 590
Hlavní autoři:	Fox, Benjamin M, Gil, Hyo-Wook, Kirkbride-Romeo, Lara, Bagchi, Rushita A, Wennersten, Sara A, Haefner, Korey R, Skrypnyk, Nataliya I, Brown, Carolyn N, Soranno, Danielle E, Gist, Katja M, Griffin, Benjamin R, Jovanovich, Anna, Reisz, Julie A, Wither, Matthew J, D'Alessandro, Angelo, Edelstein, Charles L, Clendenen, Nathan, McKinsey, Timothy A, Altmann, Christopher, Faubel, Sarah
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States 01.03.2019
Témata:	Acute Kidney Injury - complications Acute Kidney Injury - etiology Acute Kidney Injury - metabolism Animals Cardio-Renal Syndrome - diagnosis Cardio-Renal Syndrome - etiology Cardio-Renal Syndrome - metabolism Disease Models, Animal Echocardiography Energy Metabolism Heart - diagnostic imaging Heart Failure, Diastolic - diagnosis Heart Failure, Diastolic - etiology Heart Failure, Diastolic - metabolism Humans Ischemia - complications Ischemia - etiology Ischemia - metabolism Kidney - blood supply Kidney - pathology Male Metabolome Metabolomics Mice Myocardium - metabolism Myocardium - pathology Oxidative Stress acute kidney injury organ crosstalk metabolomics cardiorenal syndrome
ISSN:	1523-1755, 1523-1755
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Shrnutí:	Acute kidney injury (AKI) is a systemic disease associated with widespread effects on distant organs, including the heart. Normal cardiac function is dependent on constant ATP generation, and the preferred method of energy production is via oxidative phosphorylation. Following direct ischemic cardiac injury, the cardiac metabolome is characterized by inadequate oxidative phosphorylation, increased oxidative stress, and increased alternate energy utilization. We assessed the impact of ischemic AKI on the metabolomics profile in the heart. Ischemic AKI was induced by 22 minutes of renal pedicle clamping, and 124 metabolites were measured in the heart at 4 hours, 24 hours, and 7 days post-procedure. Forty-one percent of measured metabolites were affected, with the most prominent changes observed 24 hours post-AKI. The post-AKI cardiac metabolome was characterized by amino acid depletion, increased oxidative stress, and evidence of alternative energy production, including a shift to anaerobic forms of energy production. These metabolomic effects were associated with significant cardiac ATP depletion and with echocardiographic evidence of diastolic dysfunction. In the kidney, metabolomics analysis revealed shifts suggestive of energy depletion and oxidative stress, which were reflected systemically in the plasma. This is the first study to examine the cardiac metabolome after AKI, and demonstrates that effects of ischemic AKI on the heart are akin to the effects of direct ischemic cardiac injury.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1523-1755 1523-1755
DOI:	10.1016/j.kint.2018.10.020