02 May 2003
Med Sci Monit 2003; 9(1): 52- :: ID: 15115
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, Heart Failure, Doxorubicin, Ischemia
01 May 2022 : EditorialEditorial: Cardiovascular Complications at One Year After SARS-CoV-2 Infection are Independent of Underlying Cardiovascular Risk Factors or Severity of COVID-19
Med Sci Monit 2022; 28:e937048
04 May 2022 : Clinical ResearchEffects of Wearing Face Masks on Exercise Capacity and Ventilatory Anaerobic Threshold in Healthy Subjects ...
Med Sci Monit In Press; DOI: 10.12659/MSM.936069
27 May 2022 : Clinical ResearchFactors Associated with Falls During Hospitalization for Coronavirus Disease 2019 (COVID-19)
Med Sci Monit 2022; 28:e936547
25 May 2022 : Review articleNarrative Review of the Mechanism of Hip Prosthesis Dislocation and Methods to Reduce the Risk of Dislocation
Med Sci Monit In Press; DOI: 10.12659/MSM.935665
24 May 2022 : Clinical ResearchRemimazolam Tosilate Sedation with Adjuvant Sufentanil in Chinese Patients with Liver Cirrhosis Undergoing ...
Med Sci Monit In Press; DOI: 10.12659/MSM.936580
Most Viewed Current Articles
30 Dec 2021 : Clinical ResearchRetrospective Study of Outcomes and Hospitalization Rates of Patients in Italy with a Confirmed Diagnosis o...
Med Sci Monit 2021; 27:e935379
08 Mar 2022 : Review articleA Review of the Potential Roles of Antioxidant and Anti-Inflammatory Pharmacological Approaches for the Man...
Med Sci Monit 2022; 28:e936292
01 Nov 2020 : Review articleLong-Term Respiratory and Neurological Sequelae of COVID-19
Med Sci Monit 2020; 26:e928996