Nitric Oxide Dysregulation in Platelets from Patients with Advanced Huntington Disease
Nitric Oxide Dysregulation in Platelets from Patients with Advanced Huntington Disease
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DOI：
10.1371/journal.pone.0089745
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发表时间：
2014-02-25
期刊：
影响因子：
3.7
通讯作者：
Squitieri, Ferdinando
中科院分区：
文献类型：
--
作者：
Carrizzo, Albino;Di Pardo, Alba;Squitieri, Ferdinando
一氧化氮（NO）是一种具有生物活性的无机分子，参与调节许多生理过程，例如血流控制、血小板粘附、内分泌功能、神经传递和神经调节。在本研究中，我们首次研究了 HD 患者血小板中 NO 信号的调节。我们招募了 55 名患有明显 HD 的患者和 28 名性别和年龄匹配的健康对照者。我们的数据表明，当胰岛素刺激的 HD 血小板上清液引起 NO 介导的血管舒张作用时，NO 介导的血管舒张作用会随着病程逐渐恶化。血管舒张缺陷似乎源于 HD 患者血小板中 NO 的错误释放，并且与 eNOS 磷酸化 (Ser(1177)) 和活性受损有关。这项研究提供了关于 HD 中 NO 代谢的重要见解，并提出了这样的假设：HD 个体血小板中 NO 的减少可能是监测疾病晚期的良好工具。
Nitric oxide (NO) is a biologically active inorganic molecule involved in the regulation of many physiological processes, such as control of blood flow, platelet adhesion, endocrine function, neurotransmission and neuromodulation. In the present study, for the first time, we investigated the modulation of NO signaling in platelets of HD patients. We recruited 55 patients with manifest HD and 28 gender-and age-matched healthy controls. Our data demonstrated that NO-mediated vasorelaxation, when evoked by supernatant from insulin-stimulated HD platelets, gradually worsens along disease course. The defective vasorelaxation seems to stem from a faulty release of NO from platelets of HD patients and, it is associated with impairment of eNOS phosphorylation (Ser(1177)) and activity. This study provides important insights about NO metabolism in HD and raises the hypothesis that the decrease of NO in platelets of HD individuals could be a good tool for monitoring advanced stages of the disease.