Urine peptidome analysis in cardiorenal syndrome reflects molecular processes

Eleni Petra, Tianlin He, Vasiliki Lygirou, Agnieszka Latosinska, Harald Mischak, Antonia Vlahou, Joachim Jankowski*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

2 Citations (Web of Science)

Abstract

The cardiorenal syndrome (CRS) is defined as the confluence of heart-kidney dysfunction. This study investigates the molecular differences at the level of the urinary peptidome between CRS patients and controls and their association to disease pathophysiology. The urinary peptidome of CRS patients (n = 353) was matched for age and sex with controls (n = 356) at a 1:1 ratio. Changes in the CRS peptidome versus controls were identified after applying the Mann-Whitney test, followed by correction for multiple testing. Proteasix tool was applied to investigate predicted proteases involved in CRS-associated peptide generation. Overall, 559 differentially excreted urinary peptides were associated with CRS patients. Of these, 193 peptides were specifically found in CRS when comparing with heart failure and chronic kidney disease urinary peptide profiles. Proteasix predicted 18 proteases involved in > 1% of proteolytic cleavage events including multiple forms of MMPs, proprotein convertases, cathepsins and kallikrein 4. Forty-four percent of the cleavage events were produced by 3 proteases including MMP13, MMP9 and MMP2. Pathway enrichment analysis supported that ECM-related pathways, fibrosis and inflammation were represented. Collectively, our study describes the changes in urinary peptides of CRS patients and potential proteases involved in their generation, laying the basis for further validation.

Original languageEnglish
Article number16219
Number of pages11
JournalScientific Reports
Volume11
Issue number1
DOIs
Publication statusPublished - 10 Aug 2021

Keywords

  • CHRONIC KIDNEY-DISEASE
  • HEART-FAILURE
  • MYOCARDIAL-INFARCTION
  • RENAL DYSFUNCTION
  • PROTEIN
  • ASSOCIATION
  • DIAGNOSIS
  • COLLAGEN
  • CALCIFICATION
  • PROGRESSION

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