Kidney Response to Heart Failure: Proteomic Analysis of Cardiorenal Syndrome
Jazyk angličtina Země Švýcarsko Médium print-electronic
Typ dokumentu časopisecké články
PubMed
30235455
DOI
10.1159/000493657
PII: 000493657
Knihovny.cz E-zdroje
- Klíčová slova
- Angiotensin-II, Cardiorenal syndrome, Heart failure, Kidney function, Proteomics,
- MeSH
- albuminurie etiologie MeSH
- angiotensin konvertující enzym metabolismus MeSH
- endotel metabolismus MeSH
- extracelulární matrix - proteiny metabolismus MeSH
- kardiomegalie patofyziologie MeSH
- kardiorenální syndrom etiologie metabolismus MeSH
- krysa rodu Rattus MeSH
- ledviny chemie zranění patofyziologie MeSH
- proteom analýza metabolismus MeSH
- proteomika metody MeSH
- receptor pro konečné produkty pokročilé glykace metabolismus MeSH
- renin-angiotensin systém MeSH
- srdeční selhání komplikace MeSH
- upregulace MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- Ager protein, rat MeSH Prohlížeč
- angiotensin konvertující enzym MeSH
- extracelulární matrix - proteiny MeSH
- proteom MeSH
- receptor pro konečné produkty pokročilé glykace 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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