Abnormalities Of Mitochondrial Function In Renal Epithelial Cells Of Dogs With Chronic Heart Failure And Dogs With Cardiorenal Syndrome

Document Type

Conference Proceeding

Publication Date

1-1-2025

Publication Title

J Card Fail

Abstract

Background: Chronic heart failure (HF) is often accompanied by abnormalities of kidney function that contribute to progressive worsening of the HF state. Cardiorenal syndrome (CRS) in humans with HF is sometimes attributed to kidney underperfusion secondary to low cardiac output and/or low renal perfusion pressure, but the cellular mechanism(s) is not fully understood. We previously showed that mitochondrial (MITO) function is abnormal in cardiomyocytes of the failing heart, and it is possible that similar energetic dysfunction in the kidneys contributes to renal dysfunction in HF. In the present study, we tested the hypothesis that MITO function is abnormal in kidneys of dogs with chronic HF and dogs with CRS compared to normal (NL) dogs. Methods: MITO functional studies were performed in fresh renal epithelial cells isolated from the left kidney of 6 NL dogs, 6 HF dogs (LV ejection fraction 34±1 %) and 6 CRS dogs (LV ejection fraction 33±2%), for a total n=18 animals. HF was produced using coronary microembolizations. CRS was produced in HF dogs by unilateral nephrectomy of the right kidney and creation of a stenosis of the left renal vein sufficient to result in renal venous congestion (increasing venous pressure by 20-30 mmHg). MITO function was assessed as follows: 1) Mitochondrial ADP-stimulated state-3 respiration (ADPresp) was measured using a Strathkelvin respirometer, 2) mitochondrial complex-IV (COX-IV) activity was measured polarographically, 3) mitochondrial membrane potential (Δψm) was measured using the fluorescent cationic JC-1 dye, and 4) mitochondrial maximum rate of ATP synthesis (ATPsyn) was measured using the bioluminescent ApoSENSOR assay kit. Results: The table summarizes all MITO function measurements. ADPresp, COV-IV activity, Δψm, and ATPsyn were significantly lower in renal epithelial cells from HF dogs compared to NL dogs. Moreover, all MITO parameters were significantly lower in cells from CRS dogs when compared to NL dogs as well as to HF dogs. Conclusions: MITO function of renal epithelial cells is abnormal in HF dogs and markedly compromised in CRS dogs. MITO abnormalities likely contribute to renal dysfunction that accompanies HF. Additional investigations are needed to test if interventions that improve MITO function in the setting of HF can protect renal function or treat CRS.

Volume

31

Issue

1

First Page

245

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