Barzegar Mansoureh, Stokes Karen Y, Chernyshev Oleg, Kelley Roger E, Alexander Jonathan S
Molecular and Cellular Physiology, Ochsner-LSU Health Sciences Center, Shreveport, LA 71130-3932, USA.
Neurology, Ochsner-LSU Health Sciences Center, Shreveport, LA 71130-3932, USA.
Biomedicines. 2021 Nov 11;9(11):1667. doi: 10.3390/biomedicines9111667.
Ischemic stroke remains the leading cause of neurologically based morbidity and mortality. Current stroke treatment is limited to two classes of FDA-approved drugs: thrombolytic agents (tissue plasminogen activator (tPA)) and antithrombotic agents (aspirin and heparin), which have a narrow time-window (<4.5 h) for administration after onset of stroke symptoms. While thrombolytic agents restore perfusion, they carry serious risks for hemorrhage, and do not influence damage responses during reperfusion. Consequently, stroke therapies that can suppress deleterious effects of ischemic injury are desperately needed. Angiotensin converting enzyme-2 (ACE2) has been recently suggested to beneficially influence experimental stroke outcomes by converting the vasoconstrictor Ang II into the vasodilator Ang 1-7. In this review, we extensively discuss the protective functions of ACE2-Ang (1-7)-MasR axis of renin angiotensin system (RAS) in ischemic stroke.
缺血性中风仍然是导致神经功能缺损相关发病和死亡的主要原因。目前的中风治疗仅限于两类经美国食品药品监督管理局(FDA)批准的药物:溶栓剂(组织型纤溶酶原激活剂(tPA))和抗血栓药物(阿司匹林和肝素),这些药物在中风症状发作后的给药时间窗很窄(<4.5小时)。虽然溶栓剂可恢复灌注,但它们有严重的出血风险,并且对再灌注期间的损伤反应没有影响。因此,迫切需要能够抑制缺血性损伤有害影响的中风治疗方法。最近有研究表明,血管紧张素转换酶2(ACE2)通过将血管收缩剂血管紧张素II(Ang II)转化为血管舒张剂血管紧张素1-7(Ang 1-7),对实验性中风的预后产生有益影响。在这篇综述中,我们广泛讨论了肾素血管紧张素系统(RAS)的ACE2-Ang(1-7)-MasR轴在缺血性中风中的保护作用。