Kidney Response to Heart Failure: Proteomic Analysis of Cardiorenal Syndrome
Language English Country Switzerland Media print-electronic
Document type Journal Article
PubMed
30235455
DOI
10.1159/000493657
PII: 000493657
Knihovny.cz E-resources
- Keywords
- Angiotensin-II, Cardiorenal syndrome, Heart failure, Kidney function, Proteomics,
- MeSH
- Albuminuria etiology MeSH
- Peptidyl-Dipeptidase A metabolism MeSH
- Endothelium metabolism MeSH
- Extracellular Matrix Proteins metabolism MeSH
- Cardiomegaly physiopathology MeSH
- Cardio-Renal Syndrome etiology metabolism MeSH
- Rats MeSH
- Kidney chemistry injuries physiopathology MeSH
- Proteome analysis metabolism MeSH
- Proteomics methods MeSH
- Receptor for Advanced Glycation End Products metabolism MeSH
- Renin-Angiotensin System MeSH
- Heart Failure complications MeSH
- Up-Regulation MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Ager protein, rat MeSH Browser
- Peptidyl-Dipeptidase A MeSH
- Extracellular Matrix Proteins MeSH
- Proteome MeSH
- Receptor for Advanced Glycation End Products MeSH
BACKGROUND/AIMS: Chronic heart failure (HF) disrupts normal kidney function and leads to cardiorenal syndrome that further promotes HF progression. To identify potential participants in HF-related injury, we analyzed kidney proteome in an established HF model. METHODS: HF was induced by chronic volume overload in male HanSD rats using aorto-caval fistula. After 21 weeks, cardiac and renal functions (in-situ kidney study) and renal proteomics were studied in sham-operated (controls) and HF rats, using iTRAQ labeling and LC-MS with Orbitrap Fusion, leading to identification and quantification of almost 4000 proteins. RESULTS: Compared to controls, HF rats had cardiac hypertrophy, systemic and pulmonary congestion. Kidneys of HF rats had reduced renal blood flow, sodium excretion and urine production. While glomerular filtration rate, serum cystatin C and creatinine were still normal compared to controls, HF kidneys showed albuminuria and markedly increased tissue angiotensin-II levels (5-fold). HF kidneys (versus controls) displayed differential expression (˃1.5-fold) of 67 proteins. The most upregulated were angiotensin-converting enzyme (ACE, ˃20-fold), advanced glycosylation product-specific receptor (RAGE, 14-fold), periostin (6.8-fold), caveolin-1 (4.5-fold) and other proteins implicated in endothelial function (vWF, cavins 1-3, T-kininogen 2), proinflammatory ECM activation (MFAP4, collagen-VI, galectin-3, FHL-1, calponin) and proteins involved in glomerular filtration membrane integrity (CLIC5, ZO-1). Carboxylesterase-1D (CES1D), an enzyme that converts ACE inhibitors or sacubitril into active drugs, was also upregulated in HF kidneys. CONCLUSION: Chronic HF leads to latent kidney injury, associated with deep changes in kidney protein composition. These alterations may act in concert with intrarenal renin-angiotensin system activation and may serve as markers and/or targets to tackle cardiorenal syndrome.
BIOCEV 1st Faculty of Medicine Charles University Prague Prague Czech Republic
Institute for Clinical and Experimental Medicine Prague Czech Republic
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