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微小RNA-21是心血管疾病的治疗靶点吗?

Is miR-21 A Therapeutic Target in Cardiovascular Disease?

作者信息

Holland Antoinette, Enrick Molly, Diaz Arianna, Yin Liya

机构信息

Department of Integrative Medical Sciences, Northeast Ohio Medical University, Ohio 44272, USA.

出版信息

Int J Drug Discov Pharm. 2023 Apr;2(1):26-36. doi: 10.53941/ijddp.0201003. Epub 2023 Jan 11.

Abstract

microRNA-21 (miR-21) serves a multitude of functions at the molecular level through its regulation of messenger RNA. Previous research has sparked interest in the role of miR-21 as a potential therapeutic target in cardiovascular diseases. miR-21 expression contributes to the differentiation, proliferation, and maturation of many cell types, such as fibroblasts, endothelial cells, cardiomyocytes, and endothelial progenitor cells. The function of miR-21 depends upon its expression level in the specific cell types and downstream targets, which determine cell fate. Under pathological conditions, the expression level of miR-21 is altered, leading to abnormal gene regulation of downstream signaling and cardiovascular diseases such as hypertension, cardiac hypertrophy and fibrosis, atherosclerosis, and heart failure. Agomirs or antagomirs can be introduced into the respective tissue type to reverse or stop the progression of the disease. Exosomes in the extracellular vesicles, which mediate many cellular events with high biocompatibility, have a high potential of efficiently delivering miR-21 to their targeted cells. The critical role of miR-21 in cardiovascular disease (CVD) is indisputable, but there are controversial reports on the function of miR-21 in the same disease. This discrepancy sparks interest in better understanding the role of miR-21 in different tissues under different stages of various diseases and the mechanism of how miR-21 inhibitors work.

摘要

微小RNA-21(miR-21)通过对信使核糖核酸的调控在分子水平发挥多种功能。先前的研究引发了人们对miR-21作为心血管疾病潜在治疗靶点作用的兴趣。miR-21的表达有助于多种细胞类型的分化、增殖和成熟,如成纤维细胞、内皮细胞、心肌细胞和内皮祖细胞。miR-21的功能取决于其在特定细胞类型中的表达水平以及下游靶点,这些决定了细胞命运。在病理条件下,miR-21的表达水平会发生改变,导致下游信号传导的基因调控异常以及诸如高血压、心脏肥大和纤维化、动脉粥样硬化和心力衰竭等心血管疾病。可以将激动剂或拮抗剂导入相应的组织类型以逆转或阻止疾病进展。细胞外囊泡中的外泌体具有高生物相容性,可介导许多细胞事件,具有将miR-21高效递送至其靶细胞的巨大潜力。miR-21在心血管疾病(CVD)中的关键作用是无可争议的,但关于miR-21在同一疾病中的功能存在有争议的报道。这种差异引发了人们对更好地理解miR-21在各种疾病不同阶段不同组织中的作用以及miR-21抑制剂作用机制的兴趣。

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