OXIDATIVE STRESS RELATED PARTHANATOS OF CIRCULATING MONONUCLEAR LEUKOCYTES IN HEART FAILURE

Bárány, Tamás and Simon, Andrea and Szabó, Gergő and Benkő, Rita and Mezei, Zsuzsanna and Molnár, Levente and Becker, Dávid and Merkely, Béla Péter and Zima, Endre István and Horváth, Eszter Mária (2017) OXIDATIVE STRESS RELATED PARTHANATOS OF CIRCULATING MONONUCLEAR LEUKOCYTES IN HEART FAILURE. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY. ISSN 1942-0900 (In Press)

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Abstract

Background: The present study aims to examine the oxidative stress related activation of poly(ADP-ribose)polymerase (PARP), signs 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, body mass index matched volunteers (n=15) with normal heart function were enrolled. C-reactive protein, N-terminal pro-brain 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 significant positive correlation to PRX, OSI, leukocyte HNE, NT, PARylation and AIF translocation. Ejection fraction negatively correlated with same parameters. Among HF patients, 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.

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