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RNA interference therapy: a new solution for intracranial atherosclerosis?

机译:RNA干扰疗法:颅内动脉粥样硬化的新解决方案?

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摘要

Intracranial atherosclerotic stenosis (ICAS) of a major intracranial artery, especially middle cerebral artery (MCA), is reported to be one leading cause of ischemic stroke throughout the world. Compared with other stroke subtypes, ICAS is associated with a higher risk of recurrent stroke despite aggressive medical therapy. Increased understanding of the pathophysiology of ICAS has highlighted several possible targets for therapeutic interventions. Both luminal stenosis and plaque components of ICAS have been found to be associated with ischemic stroke based a post-mortem study. Recent application of high-resolution magnetic resonance imaging (HRMRI) in evaluating ICAS provides new insight into the vascular biology of plaque morphology and component. High signal on T1-weighted fat-suppressed images (HST1) within MCA plaque of HRMRI, highly suggested of fresh or recent intraplaque hemorrhage, has been found to be associated with ipsilateral brain infarction. Thus, the higher prevalence of intraplaque hemorrhage and neovasculature in symptomatic patients with MCA stenosis may provide a potential target for plaque stabilization. We hypothesize that RNA interference (RNAi) therapy delivered by modified nanoparticles may achieve in vivo biomedical imaging and targeted therapy. With the rapid developments in studies about therapeutic and diagnostic nanomaterials, future studies further exploring the molecular biology of atherosclerosis may provide more drug targets for plaque stabilization.
机译:据报道,全世界主要的颅内动脉,特别是大脑中动脉(MCA)的颅内动脉粥样硬化狭窄(ICAS)是导致缺血性中风的主要原因之一。与其他中风亚型相比,尽管进行了积极的药物治疗,ICAS仍具有较高的复发性中风风险。对ICAS的病理生理学的日益了解突出了治疗干预的几个可能目标。根据事后研究,发现ICAS的管腔狭窄和斑块成分均与缺血性中风有关。高分辨率磁共振成像(HRMRI)在评估ICAS中的最新应用为斑块形态和成分的血管生物学提供了新的见识。已发现HRMRI的MCA斑块内T1加权脂肪抑制图像(HST1)上的高信号(强烈暗示有新鲜或近期斑块内出血)与同侧脑梗死有关。因此,有症状的MCA狭窄患者的斑块内出血和新脉管系统患病率较高,可能为斑块稳定提供潜在的靶标。我们假设由修饰的纳米粒子提供的RNA干扰(RNAi)治疗可以实现体内生物医学成像和靶向治疗。随着治疗和诊断纳米材料研究的迅速发展,未来进一步研究动脉粥样硬化分子生物学的研究可能会为斑块稳定提供更多的药物靶标。

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