Ischemic stroke remains the fifth cause of death, as reported worldwide annually. Endothelial dysfunction (ED) manifesting with lower nitric oxide (NO) bioavailability leads to increased vascular tone, inflammation, and platelet activation and remains among the major contributors to cardiovascular diseases (CVD). Moreover, temporal fluctuations in the NO bioavailability during ischemic stroke point to its key role in the cerebral blood flow (CBF) regulation, and some data suggest that they may be responsible for the maintenance of CBF within the ischemic penumbra in order to reduce infarct size. Several years ago, the inhibitory role of the platelet NO production on a thrombus formation has been discovered, which initiated the era of extensive studies on the platelet-derived nitric oxide (PDNO) as a platelet negative feedback regulator. Very recently, Radziwon-Balicka et al. discovered two subpopulations of human platelets, based on the expression of the endothelial nitric oxide synthase (eNOS-positive or eNOS-negative platelets, respectively). The e-NOS-negative ones fail to produce NO, which attenuates their cyclic guanosine monophosphate (cGMP) signaling pathway and—as result—promotes adhesion and aggregation while the e-NOS-positive ones limit thrombus formation. Asymmetric dimethylarginine (ADMA), a competitive NOS inhibitor, is an independent cardiovascular risk factor, and its expression alongside with the enzymes responsible for its synthesis and degradation was recently shown also in platelets. Overproduction of ADMA in this compartment may increase platelet activation and cause endothelial damage, additionally to that induced by its plasma pool. All the recent discoveries of diverse eNOS expression in platelets and its role in regulation of thrombus formation together with studies on the NOS inhibitors have opened a new chapter in translational medicine investigating the onset of acute cardiovascular events of ischemic origin. This translative review briefly summarizes the role of platelets and NO biotransformation in the pathogenesis and clinical course of ischemic stroke.

中文翻译：

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血小板和一氧化氮的生物转化在缺血性卒中中的作用：从长凳到床边的翻译回顾。

缺血性中风仍然是死亡的第五大原因，全球每年都有报道。一氧化氮（NO）生物利用度较低的内皮功能障碍（ED）导致血管紧张度，炎症和血小板活化增加，并且仍然是心血管疾病（CVD）的主要贡献者。此外，缺血性中风期间NO生物利用度的时间波动表明其在脑血流量（CBF）调节中起关键作用，一些数据表明，它们可能是缺血半影内CBF维持的原因，以减少梗死面积。几年前，已经发现血小板NO的产生对血栓形成的抑制作用，这开启了对血小板源性一氧化氮（PDNO）作为血小板负反馈调节剂的广泛研究的时代。最近，Radziwon-Balicka等人。根据内皮型一氧化氮合酶（分别为eNOS阳性或eNOS阴性的血小板）的表达，发现了人类血小板的两个亚群。e-NOS阴性的人无法产生NO，从而减弱了其环状鸟苷单磷酸（cGMP）信号传导途径，从而促进了粘附和聚集，而e-NOS阳性的人则限制了血栓形成。竞争性NOS抑制剂非对称二甲基精氨酸（ADMA）是独立的心血管危险因素，最近在血小板中也显示了其表达以及负责其合成和降解的酶的表达。除了其血浆库所引起的损害外，在该隔室中过量产生的ADMA可能会增加血小板活化并引起内皮损伤。所有最近在血小板中表达不同eNOS的发现及其在血栓形成调节中的作用以及对NOS抑制剂的研究，为转化医学研究缺血性急性心血管事件的发作开辟了新篇章。这篇综述简要总结了血小板和NO的生物转化在缺血性中风的发病机制和临床过程中的作用。