Protective effects of PARP-1 knockout on dyslipidemia-induced autonomic and vascular dysfunction in ApoE mice: effects on eNOS and oxidative stress.
Protective effects of PARP-1 knockout on dyslipidemia-induced autonomic and vascular dysfunction in ApoE mice: effects on eNOS and oxidative stress.
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DOI：
10.1371/journal.pone.0007430
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发表时间：
2009-10-13
期刊：
影响因子：
3.7
通讯作者：
Boulares AH
中科院分区：
文献类型：
--
作者：
Hans CP;Feng Y;Naura AS;Zerfaoui M;Rezk BM;Xia H;Kaye AD;Matrougui K;Lazartigues E;Boulares AH
本研究的目的是探讨聚（ADP-核糖）聚合酶（PARP）-1 在血脂异常相关的血管功能障碍以及自主神经系统失调中的作用。喂食高脂肪饮食的载脂蛋白（ApoE）−/−小鼠被用作动脉粥样硬化模型。使用遥测技术测量有意识的小鼠的血管和自主神经功能。研究表明，PARP-1 在血脂异常相关的血管和自主神经功能障碍中发挥着重要作用。通过基因敲除对该酶的抑制部分恢复了 ApoE−/− 小鼠的压力反射敏感性，而不影响基线心率和动脉压，并且还改善了选择性阻断自主神经系统后的心率反应。 PARP-1 基因缺失对血脂异常诱导的内皮功能障碍的保护作用与 eNOS 活性的保留有关。血脂异常诱导的 PARP-1 激活伴随着氧化组织损伤，iNOS 表达增加和随后的蛋白质硝化证明了这一点。 PARP-1 基因缺失逆转了这些影响，表明 PARP-1 可能通过促进氧化组织损伤而导致血管和自主神经病变。此外，抑制这种氧化损伤可能是 PARP-1 基因缺失对血管和自主神经功能的保护作用的原因。这项研究表明，PARP-1 参与血脂异常介导的自主神经系统失调，并且 PARP-1 基因缺失使自主神经和血管功能障碍正常化。 eNOS 活性的维持可能与 PARP-1 基因缺失对血脂异常引起的内皮功能障碍的保护作用有关。
The aims of this study were to investigate the role of poly(ADP-ribose) polymerase (PARP)-1 in dyslipidemia-associated vascular dysfunction as well as autonomic nervous system dysregulation. Apolipoprotein (ApoE)−/− mice fed a high-fat diet were used as a model of atherosclerosis. Vascular and autonomic functions were measured in conscious mice using telemetry. The study revealed that PARP-1 plays an important role in dyslipidemia-associated vascular and autonomic dysfunction. Inhibition of this enzyme by gene knockout partially restored baroreflex sensitivity in ApoE−/− mice without affecting baseline heart-rate and arterial pressure, and also improved heart-rate responses following selective blockade of the autonomic nervous system. The protective effect of PARP-1 gene deletion against dyslipidemia-induced endothelial dysfunction was associated with preservation of eNOS activity. Dyslipidemia induced PARP-1 activation was accompanied by oxidative tissue damage, as evidenced by increased expression of iNOS and subsequent protein nitration. PARP-1 gene deletion reversed these effects, suggesting that PARP-1 may contribute to vascular and autonomic pathologies by promoting oxidative tissue injury. Further, inhibition of this oxidative damage may account for protective effects of PARP-1 gene deletion on vascular and autonomic functions. This study demonstrates that PARP-1 participates in dyslipidemia-mediated dysregulation of the autonomic nervous system and that PARP-1 gene deletion normalizes autonomic and vascular dysfunctions. Maintenance of eNOS activity may be associated with the protective effect of PARP-1 gene deletion against dyslipidemia-induced endothelial dysfunction.
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DOI：
10.1111/j.1440-1681.2007.04719.x
发表时间：
2007-12-01
影响因子：
2.9
作者：
Liao, Song-Jie;Lin, Li;Chen, Alex F.
通讯作者：
Chen, Alex F.
影响因子：
6.1
作者：
Benkö, R;Pacher, P;Szabó, C
通讯作者：
Szabó, C
影响因子：
2.1
作者：
Gava, Agata L.;Peotta, Veronica A.;Meyrelles, Silvana S.
通讯作者：
Meyrelles, Silvana S.
影响因子：
10.8
作者：
Crauwels, HM;Van Hove, CE;Bult, H
通讯作者：
Bult, H
影响因子：
24.3
作者：
Naura, A. S.;Datta, R.;Boulares, A. H.
通讯作者：
Boulares, A. H.