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治疗腹主动脉瘤的分子药理学方法。

Molecular Pharmacological Approaches for Treating Abdominal Aortic Aneurysm.

作者信息

Miyake Takashi, Miyake Tetsuo, Kurashiki Tomohiro, Morishita Ryuichi

机构信息

Department of Clinical Gene Therapy, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.

出版信息

Ann Vasc Dis. 2019 Jun 25;12(2):137-146. doi: 10.3400/avd.ra.18-00076.

Abstract

Abdominal aortic aneurysm (AAA) is considered to be a potent life-threatening disorder in elderly individuals. Although many patients with a small AAA are detected during routine abdominal screening, there is no effective therapeutic option to prevent the progression or regression of AAA in the clinical setting. Recent advances in molecular biology have led to the identification of several important molecules, including microRNA and transcription factor, in the process of AAA formation. Regulation of these factors using nucleic acid drugs is expected to be a novel therapeutic option for AAA. Nucleic acid drugs can bind to target factors, mRNA, microRNA, and transcription factors in a sequence-specific fashion, resulting in a loss of function of the target molecule at the transcriptional or posttranscriptional level. Of note, inhibition of a transcription factor using a decoy strategy effectively suppresses experimental AAA formation, by regulating the expression of several genes associated with the disease progression. This review focuses on recent advances in molecular therapy of using nucleic acid drugs to treat AAA.

摘要

腹主动脉瘤(AAA)被认为是老年人群中一种严重威胁生命的疾病。尽管许多小AAA患者是在常规腹部筛查中被发现的,但在临床环境中,尚无有效的治疗方法来预防AAA的进展或使其消退。分子生物学的最新进展已导致在AAA形成过程中鉴定出几种重要分子,包括微小RNA和转录因子。使用核酸药物调节这些因子有望成为AAA的一种新型治疗选择。核酸药物可以以序列特异性方式与靶因子、信使核糖核酸(mRNA)、微小RNA和转录因子结合,导致靶分子在转录或转录后水平上功能丧失。值得注意的是,通过调节与疾病进展相关的几个基因的表达,使用诱饵策略抑制转录因子可有效抑制实验性AAA的形成。本综述重点关注使用核酸药物治疗AAA的分子疗法的最新进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8722/6600097/c0b7ea252622/avd-12-2-ra.18-00076-figure01.jpg

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