Activation of the NF-κB Signalling Pathway by Angiotensin II Aggravates Renal Inflammatory Injury During...

Area of Science:

• Cardiovascular Physiology
• Renal Medicine
• Extracorporeal Life Support

Background:

• Non-pulsatile perfusion is standard in extracorporeal life support (ECLS), but linked to renal injury.
• Physiological pulsatile perfusion may offer renal protection.

Purpose of the Study:

• To investigate the differential effects of pulsatile versus non-pulsatile perfusion on renal injury in an ECLS model.
• To explore the underlying molecular mechanisms, including Angiotensin II (Ang II) and NF-κB signaling.

Main Methods:

• Utilized a rat ECLS model with veno-arterial (VA) and veno-venous (VV) ECMO to simulate non-pulsatile and pulsatile perfusion.
• Assessed renal injury biomarkers (BUN, Scr, KIM-1, Cys-C) and molecular pathways via transcriptomics, Western blotting, and qPCR.
• Administered captopril in a subgroup to evaluate Ang II's role in non-pulsatile perfusion.

Main Results:

• Pulsatile perfusion demonstrated significantly lower renal injury biomarkers (BUN, Scr, KIM-1, Cys-C) compared to non-pulsatile perfusion.
• Non-pulsatile perfusion showed increased Ang II expression and enriched NF-κB signaling, correlating with inflammation.
• Captopril treatment in the non-pulsatile group reduced Ang II, inflammation, and NF-κB activation.

Conclusions:

• Pulsatile perfusion in ECLS is associated with reduced renal injury and inflammation, potentially via Ang II modulation.
• Captopril may mitigate renal injury and inflammation during non-pulsatile perfusion by affecting NF-κB.
• Findings are preliminary and require validation in clinical models.