Pharmacologic inhibition of poly(adenosine diphosphate-ribose) polymerase may represent a novel therapeutic approach in chronic heart failure.
Pharmacologic inhibition of poly(adenosine diphosphate-ribose) polymerase may represent a novel therapeutic approach in chronic heart failure.
复制标题
聚（腺苷二磷酸核糖）聚合酶的药理学抑制可能代表慢性心力衰竭的新治疗方法。
DOI：
10.1016/s0735-1097(02)02062-4
复制
发表时间：
2002
影响因子：
24
通讯作者：
Szabó,Csaba
中科院分区：
文献类型：
--
作者：
Pacher,Pál;Liaudet,Lucas;Mabley,Jong;Komjáti,Katalin;Szabó,Csaba
目的研究一种新型的超强效聚乙烯（poly）（腺苷二磷酸-核糖）聚合酶（PARP）抑制剂PJ 34对慢性心力衰竭（CHF）大鼠模型中心脏和内皮功能障碍的影响。背景在与氧化应激相关的各种病理生理条件下，包括心肌再灌注损伤，心脏移植、中风、休克和糖尿病。方法通过慢性结扎冠状动脉左前降支在Wistar大鼠中诱导慢性心力衰竭。术后10周测量左心室（LV）功能和离体血管收缩力和舒张力。Nitrotyrosine（NT）的形成和PARP激活进行了检测，通过免疫组化。Results慢性心力衰竭诱导增加NT的形成和PARP激活在心肌和壁内血管，降低LV性能，和受损的血管舒张主动脉环。PJ 34显着降低心肌PARP激活，但不NT的形成，并改善心功能不全和血管relaxation.ConclusionsPoly（ADP-核糖）聚合酶抑制代表了一种新的方法，为CHF的实验治疗。
ObjectivesWe investigated the effects of a novel ultrapotent poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitor, PJ34, on cardiac and endothelial dysfunction in a rat model of chronic heart failure (CHF).BackgroundOveractivation of the nuclear enzyme PARP importantly contributes to the development of cell dysfunction and tissue injury in various pathophysiologic conditions associated with oxidative stress, including myocardial reperfusion injury, heart transplantation, stroke, shock, and diabetes.MethodsChronic heart failure was induced in Wistar rats by chronic ligation of the left anterior descending coronary artery. Left ventricular (LV) function and ex vivo vascular contractility and relaxation were measured 10 weeks after the surgery. Nitrotyrosine (NT) formation and PARP activation were detected by immunohistochemistry.ResultsChronic heart failure induced increased NT formation and PARP activation in the myocardium and intramural vasculature, depressed LV performance, and impaired vascular relaxation of aortic rings. PJ34 significantly decreased myocardial PARP activation but not NT formation, and improved both cardiac dysfunction and vascular relaxation.ConclusionsPoly(ADP-ribose) polymerase inhibition represents a novel approach for the experimental treatment of CHF.