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Urine peptidome analysis in cardiorenal syndrome reflects molecular processes
Eleni Petra1,2, Tianlin He1,3, Vasiliki Lygirou2
1Institute for Molecular Cardiovascular Research, RWTH Aachen University Hospital, Pauwelsstraße 30, 52074, Aachen, Germany.
Insights
This study reveals distinct urinary peptide profiles in cardiorenal syndrome (CRS) patients, identifying specific peptides and proteases linked to heart and kidney dysfunction. These findings offer new insights into CRS pathophysiology.
Area of Science:
- Biochemistry
- Molecular Biology
- Nephrology
Background:
- Cardiorenal syndrome (CRS) involves complex heart-kidney dysfunction.
- Understanding the molecular underpinnings of CRS is crucial for diagnosis and treatment.
- The urinary peptidome offers a window into systemic physiological changes.
Purpose of the Study:
- To investigate molecular differences in the urinary peptidome between CRS patients and controls.
- To identify specific peptides associated with CRS pathophysiology.
- To explore the role of proteases in generating CRS-associated peptides.
Main Methods:
- Comparative analysis of urinary peptidomes from CRS patients (n=353) and matched controls (n=356).
- Statistical analysis using the Mann-Whitney test with correction for multiple testing.
- Protease prediction using the Proteasix tool and pathway enrichment analysis.
Main Results:
- 559 differentially excreted urinary peptides were identified in CRS patients.
- 193 peptides were unique to CRS compared to heart failure and chronic kidney disease profiles.
- 18 proteases were predicted to be involved, with MMP13, MMP9, and MMP2 responsible for 44% of cleavage events.
- ECM-related pathways, fibrosis, and inflammation were significantly represented.
Conclusions:
- The study characterizes unique urinary peptide changes in CRS patients.
- Key proteases, including MMPs, are implicated in CRS-associated peptide generation.
- These findings provide a basis for further validation and potential diagnostic markers for CRS.
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.
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