02 May 2003
Poly(ADP-ribose) polymerase (PARP) and chronic heart failure
P. Pacher, C. SzaboMed Sci Monit 2003; 9(1): 52-0 :: ID: 15115
Abstract
Overactivation of the nuclear enzyme PARP importantly contributes to the development of cell dysfunction and tissue injury in various pathophysiological conditions associated with oxidative stress, including myocardial reperfusion injury, heart transplantation, stroke, shock and diabetes. We investigated the effects of a novel ultrapotent poly(ADP-ribose) polymerase (PARP) inhibitors PJ34 and INO1001, on cardiac and endothelial dysfunction in rat models of chronic heart failure (CHF) induced by either chronic ligation of the left anterior descending coronary artery or by the administration of the cytotoxic drug doxorubicin (DOX). In the CHF model, left ventricular function and ex vivo vascular contractility and relaxation were measured 10 or 8 weeks after the surgery. Nitrotyrosine (NT) formation and PARP activation were detected by immunohistochemistry. CHF and DOX induced increased NT formation and PARP activation in the myocardium and intramural vasculature, depressed left ventricular performance and impaired vascular relaxation of aortic rings. PJ34 and INO1001 significantly improved both cardiac dysfunction and vascular relaxation and delayed CHF- and DOX associated mortality. Thus, PARP activation plays a key role in the pathogenesis of various forms of chronic heart failure. References: 1.Virág L, Szabó C: The therapeutic potential of PARP inhibition. Pharmacological Reviews, 2002; 54: 375-429 2.Soriano FG, Virág L, Jagtap P et al: Diabetic endothelial dysfunction: the role of poly (ADP-ribose) polymerase activation. Nature Medicine, 2001; 7: 108-113 3.Pacher P, Liaudet L, Soriano FG et al: The role of poly(ADP-ribose) polymerase in the development of chronic heart failure. J Am Coll Cardiol, 2002; 40: 1006-1016
Keywords: myocardial dysfunction, peroxynitrite, Ischemia
Editorial
01 May 2024 : Editorial
Editorial: First Regulatory Approval for Adoptive Cell Therapy with Autologous Tumor-Infiltrating Lymphocytes (TILs) – Lifileucel (Amtagvi)DOI: 10.12659/MSM.944927
Med Sci Monit 2024; 30:e944927
In Press
12 Mar 2024 : Clinical Research
Preoperative Blood Transfusion Requirements for Hemorrhoidal Severe Anemia: A Retrospective Study of 128 Pa...Med Sci Monit In Press; DOI: 10.12659/MSM.943126
12 Mar 2024 : Clinical Research
Tissue Inhibitors of Metalloproteinase 1 (TIMP-1) and 3 (TIMP-3) as New Markers of Acute Kidney Injury Afte...Med Sci Monit In Press; DOI: 10.12659/MSM.943500
12 Mar 2024 : Review article
Optimizing Behçet Uveitis Management: A Review of Personalized Immunosuppressive StrategiesMed Sci Monit In Press; DOI: 10.12659/MSM.943240
12 Mar 2024 : Clinical Research
Metabolomic Alterations in Methotrexate Treatment of Moderate-to-Severe PsoriasisMed Sci Monit In Press; DOI: 10.12659/MSM.943360
Most Viewed Current Articles
17 Jan 2024 : Review article
Vaccination Guidelines for Pregnant Women: Addressing COVID-19 and the Omicron VariantDOI :10.12659/MSM.942799
Med Sci Monit 2024; 30:e942799
14 Dec 2022 : Clinical Research
Prevalence and Variability of Allergen-Specific Immunoglobulin E in Patients with Elevated Tryptase LevelsDOI :10.12659/MSM.937990
Med Sci Monit 2022; 28:e937990
16 May 2023 : Clinical Research
Electrophysiological Testing for an Auditory Processing Disorder and Reading Performance in 54 School Stude...DOI :10.12659/MSM.940387
Med Sci Monit 2023; 29:e940387
01 Jan 2022 : Editorial
Editorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Pa...DOI :10.12659/MSM.935952
Med Sci Monit 2022; 28:e935952