MicroRNA-21与颈动脉疾病和缺血性卒中的关联:从病理生理学到临床意义和潜在治疗

IF 4.4 Q1 Medicine
Aleksandar Sič, Marko Atanasković, Alyan Ahmed, Ivan Petrović, Filip Simović, Boris Burnjaković, Una Tonković, Aarish Manzar, Simra Shadab, Selena Gajić, Danka Bjelić, Vidna Karadžić Ristanović, Marko Baralić
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引用次数: 0

摘要

缺血性脑卒中是世界范围内发病率和死亡率的主要原因之一,颈动脉粥样硬化是其主要病因。MicroRNA-21 (miR-21)调节负责血管变化和缺血性脑损伤的细胞内信号通路,被认为是一种潜在的诊断和预后生物标志物。它改变巨噬细胞(MΦ)和血管平滑肌细胞的活性,引起炎症并影响动脉粥样硬化斑块的稳定性。巨噬细胞中miR-21的缺乏会刺激炎症反应和斑块生长。它既促进细胞外基质的合成,稳定斑块,又促进纤维蛋白帽的降解,导致斑块不稳定。miR-21对内皮细胞的作用不同:它既刺激NO·合成又刺激炎症。在缺血性卒中期间,miR-21通过调节缺血后炎症和保护血脑屏障的完整性显示出神经保护作用。靶向miR-21的治疗在实验模型中显示出潜力,但它需要细胞特异性递送和精确的时间。进一步的研究工作应侧重于miR-21对不同细胞类型的影响,以及开发用于诊断和治疗应用的新技术。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The Association of MicroRNA-21 with Carotid Artery Disease and Ischemic Stroke: From Pathophysiology to Clinical Implications and Potential Therapy.

Ischemic stroke is one of the leading causes of morbidity and mortality worldwide, with carotid atherosclerosis being its key etiological factor. MicroRNA-21 (miR-21) regulates intracellular signal pathways responsible for vascular changes and ischemic brain injury, and is recognized as a potential diagnostic and prognostic biomarker. It modifies the activity of macrophages (MΦ) and vascular smooth muscle cells, causing inflammation and affecting the stability of atherosclerotic plaques. A deficiency of miR-21 in macrophages stimulates the inflammatory response and plaque growth. It promotes both the synthesis of extracellular matrix, stabilizing the plaque, and the degradation of the fibrin cap, which leads to plaque instability. The effect of miR-21 on endothelial cells differs: it stimulates both NO· synthesis and inflammation. During ischemic stroke, miR-21 demonstrates neuroprotective effects by modulating post-ischemic inflammation and protecting the integrity of the blood-brain barrier. Therapy targeting miR-21 shows potential in experimental models, but it requires cell-specific delivery and precise timing. Further research efforts should focus on the effects of miR-21 on different cell types, as well as the development of new technologies for diagnostic and therapeutic applications.

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