Oxidative Stress-Related Parthanatos of Circulating Mononuclear Leukocytes in Heart Failure.

Tamás Bárány,Gergő Szabó,Dávid Becker,Eszter M Horváth,Endre Zima,Andrea Simon,Rita Benkő,Béla Merkely,Zsuzsanna Mezei,Levente Molnár

doi:10.1155/2017/1249614

Abstract

Background The present study aims to examine the oxidative stress-related activation of poly(ADP-ribose) polymerase (PARP), a cause of parthanatos in circulating mononuclear leukocytes of patients with chronic heart failure (CHF), that was rarely investigated in the human setting yet. Methods Patients with CHF (n = 20) and age- and body mass index-matched volunteers (n = 15) with a normal heart function were enrolled. C-reactive protein, N-terminal probrain-type natriuretic peptide (pro-BNP), plasma total peroxide level (PRX), plasma total antioxidant capacity (TAC), oxidative stress index (OSI), leukocyte lipid peroxidation (4-hydroxynonenal; HNE), protein tyrosine nitration (NT), poly(ADP-ribosyl)ation (PARylation), and apoptosis-inducing factor (AIF) translocation were measured in blood samples of fasting subjects. Results Plasma PRX, leukocyte HNE, NT, PARylation, and AIF translocation were significantly higher in the heart failure group. Pro-BNP levels in all study subjects showed a significant positive correlation to PRX, OSI, leukocyte HNE, NT, PARylation, and AIF translocation. Ejection fraction negatively correlated with the same parameters. Among HF patients, a positive correlation of pro-BNP with PRX, OSI, and PARylation was still present. Conclusions Markers of oxidative-nitrative stress, PARP activation, and AIF translocation in blood components showed correlation to reduced cardiac function and the clinical appearance of CHF. These results may reinforce the consideration of PARP inhibition as a potential therapeutic target in CHF.

Highlights

Heart failure as the outcome of a variety of cardiovascular diseases implies increasing burden for global healthcare systems [1]
The median proBNP of control group is slightly elevated according to exclusionary cut-off point mentioned in the actual guideline of the European Society of Cardiology (125 pg/mL); these subjects showed no clinical signs of cardiac failure so the elevation of pro-Brain natriuretic peptide (BNP) is most probably due to other conditions [9] (Table 1)
Analyzing the same relationships in the CHF group only showed that plasma peroxide level (PRX) level, oxidative stress index (OSI), and poly(ADP-ribose) polymerase (PARP) activity in circulating leukocytes positively correlate with pro-BNP levels of the chronic heart failure patients. These results suggest a positive correlation of oxidative stress and PARP activation, with the actual clinical appearance of cardiac decompensation reflecting the severity of the chronic heart failure

Summary

Introduction

Heart failure as the outcome of a variety of cardiovascular diseases implies increasing burden for global healthcare systems [1]. The present study aims to examine the oxidative stress-related activation of poly(ADP-ribose) polymerase (PARP), a cause of parthanatos in circulating mononuclear leukocytes of patients with chronic heart failure (CHF), that was rarely investigated in the human setting yet. Pro-BNP levels in all study subjects showed a significant positive correlation to PRX, OSI, leukocyte HNE, NT, PARylation, and AIF translocation. Markers of oxidative-nitrative stress, PARP activation, and AIF translocation in blood components showed correlation to reduced cardiac function and the clinical appearance of CHF. These results may reinforce the consideration of PARP inhibition as a potential therapeutic target in CHF

Methods

Results

Discussion

Conclusion