Restoration of the endothelial function in the aortic rings of apolipoprotein E deficient mice by pharmacological inhibition of the nuclear enzyme poly(ADP-ribose) polymerase
Restoration of the endothelial function in the aortic rings of apolipoprotein E deficient mice by pharmacological inhibition of the nuclear enzyme poly(ADP-ribose) polymerase
复制标题
DOI：
10.1016/j.lfs.2004.04.007
复制
发表时间：
2004-07-23
期刊：
影响因子：
6.1
通讯作者：
Szabó, C
中科院分区：
文献类型：
--
作者：
Benkö, R;Pacher, P;Szabó, C
氧化剂介导的核酶聚（ADP-核糖）聚合酶（PARP）的激活在内皮功能障碍的发生和各种心血管疾病的发病机制中发挥作用。本研究的目的是调查 PARP 的激活是否会导致载脂蛋白 E (ApoE) 缺陷小鼠发生内皮功能障碍。我们测试了 PARP 抑制是否可以阻止内皮功能障碍的发展，以及是否可以恢复已确定内皮功能障碍的血管的功能。 ApoE 缺陷小鼠在接受或不接受 INO-1001 治疗的情况下保持高脂肪饮食 12 周。使用 PARP 抑制剂 INO-100 进行长期治疗可降低 ApoE 缺陷小鼠胸主动脉内皮功能障碍（血管舒张乙酰胆碱的能力）的程度。此外，用 PAR-P 抑制剂对患有内皮功能障碍的 ApoE 缺陷小鼠的血管进行体外培养，可显着提高环松弛乙酰胆碱的能力。我们得出的结论是，ApoE 缺陷小鼠内皮细胞中发生的早期动脉粥样硬化功能改变至少部分是可逆的，并且依赖于内皮细胞中核酶 PARP 的激活。 (C) 2004 Elsevier Inc. 保留所有权利。
Oxidant-mediated activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) plays a role in the development of endothelial dysfunction and the pathogenesis of various cardiovascular diseases. The aim of the current study was to investigate whether activation of PARP contributes to the development of endothelial dysfunction in the apolipoprotein E (ApoE) deficient mice. We tested whether PARP inhibition prevents the development of endothelial dysfunction and whether it restores function in vessels with established endothelial dysfunction. ApoE deficient mice were kept on high-fat diet for 12 weeks with and without INO- 1001 treatment. Chronic treatment with the PARP inhibitor INO-100 reduced the degree of the endothelial dysfunction (the ability of the vessel to relax to acetylcholine) in the thoracic aortae of ApoE deficient mice. In addition, in vitro incubation of vessels from ApoE deficient mice with established endothelial dysfunction with the PAR-P inhibitor acutely improved the ability of the rings to relax to acetylcholine. We conclude that the early atherosclerotic functional alterations that develop in the endothelium of the ApoE deficient mice are, at least in part, reversible, and are dependent on the activation of the nuclear enzyme PARP in the endothelial cells. (C) 2004 Elsevier Inc. All rights reserved.