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Pro-Apoptotic Effects of Plasma from Patients with Cardiorenal Syndrome on Human Tubular Cells
Grazia Maria Virzì1, Massimo de Cal, Sonya Day
1Department of Nephrology, Dialysis and Transplant, San Bortolo Hospital, Vicenza, Italy.
Background:
The pathophysiology of Cardiorenal Syndrome Type 1 (CRS1) is widely studied, although the mechanisms by which renal tubular epithelial cells (TECs) cease to proliferate and embark upon terminal differentiation, following the initial insult of heart failure (HF), remain a key target. This study seeks to provide insight into the pathophysiological pathways in CRS1; we evaluated in vitro the effects of CRS1 plasma on TECs.
Methods:
We enrolled 40 acute HF patients and 15 controls (CTR) without HF or acute kidney injury (AKI). Ten out of 40 HF patients exhibited AKI at the time of admission for HF or developed AKI during hospitalization and were classified as CRS1. In vitro, cell viability, DNA fragmentation and caspase-3 levels were investigated in TECs incubated with HF, CRS1, and CTR plasma. We assessed inflammatory cytokines and NGAL expression at the gene and protein levels.
Results:
We observed a marked pro-apoptotic activity and a significantly increased in vitro level of apoptosis in TECs incubated with plasma from CRS1 patients compared to HF and CTR (p < 0.01). In the CRS1 group, the mRNA expression of IL-6, IL-18 and NGAL resulted significantly higher in TECs incubated with CRS1 plasma compared with those incubated with plasma from HF and CTR (p < 0.01). IL-6, IL-18, NGAL, and RANTES levels were significantly higher in TECs supernatant incubated with CRS1 plasma compared with HF patients and CTR plasma (p < 0.01).
Conclusion:
In vitro exposure to plasma from CRS1 patients altered the expression profile of TECs characterized by increases in proinflammatory mediators, release of tubular damage markers, and apoptosis.
Insights
Plasma from patients with cardiorenal syndrome type 1 (CRS1) induces apoptosis and inflammation in renal tubular epithelial cells (TECs). This suggests CRS1 plasma alters TECs, contributing to kidney damage in heart failure (HF).
Area of Science:
- Nephrology
- Cardiology
- Cell Biology
Background:
- Cardiorenal Syndrome Type 1 (CRS1) pathophysiology involves heart failure (HF) impacting kidneys.
- Mechanisms of renal tubular epithelial cell (TEC) dysfunction in CRS1 are not fully understood.
- Understanding TEC response to HF-related plasma changes is crucial for CRS1 insights.
Purpose of the Study:
- To investigate the in vitro effects of plasma from CRS1 patients on TECs.
- To elucidate the pathophysiological pathways contributing to TEC alterations in CRS1.
Main Methods:
- Collected plasma from 40 acute HF patients (10 with AKI/CRS1) and 15 controls.
- Incubated TECs with plasma from CRS1, HF, and control groups.
- Assessed TEC viability, apoptosis (DNA fragmentation, caspase-3), and inflammatory markers (IL-6, IL-18, NGAL, RANTES) at gene and protein levels.
Main Results:
- CRS1 plasma significantly increased TEC apoptosis compared to HF and control plasma (p < 0.01).
- mRNA expression of IL-6, IL-18, and NGAL was significantly higher in TECs exposed to CRS1 plasma (p < 0.01).
- Supernatant levels of IL-6, IL-18, NGAL, and RANTES were significantly elevated in TECs incubated with CRS1 plasma (p < 0.01).
Conclusions:
- In vitro exposure to CRS1 patient plasma induces significant apoptosis in TECs.
- CRS1 plasma alters TEC expression profiles, increasing proinflammatory mediators and tubular damage markers.
- These findings highlight plasma-mediated TEC dysfunction as a key mechanism in CRS1 pathophysiology.
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