长链非编码 RNA 作为自噬相关心血管疾病的治疗靶点：分子机制和治疗策略的综述。

LncRNAs as Therapeutic Targets for Autophagy-involved Cardiovascular Diseases: A Review of Molecular Mechanism and T herapy Strategy.

机构信息

Department of Pediatric Cardiology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China.

Department of Pediatric Cardiothoracic Surgery, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.

出版信息

Curr Med Chem. 2021;28(9):1796-1814. doi: 10.2174/0929867327666200320161835.

DOI:10.2174/0929867327666200320161835

PMID:32196441

Abstract

BACKGROUND

Cardiovascular diseases (CVDs) remain the leading cause of death worldwide. The concept of precision medicine in CVD therapy today requires the incorporation of individual genetic and environmental variability to achieve personalized disease prevention and tailored treatment. Autophagy, an evolutionarily conserved intracellular degradation process, has been demonstrated to be essential in the pathogenesis of various CVDs. Nonetheless, there have been no effective treatments for autophagy- involved CVDs. Long noncoding RNAs (lncRNAs) are noncoding RNA sequences that play versatile roles in autophagy regulation, but much needs to be explored about the relationship between lncRNAs and autophagy-involved CVDs.

SUMMARY

Increasing evidence has shown that lncRNAs contribute considerably to modulate autophagy in the context of CVDs. In this review, we first summarize the current knowledge of the role lncRNAs play in cardiovascular autophagy and autophagy-involved CVDs. Then, recent developments of antisense oligonucleotides (ASOs) designed to target lncRNAs to specifically modulate autophagy in diseased hearts and vessels are discussed, focusing primarily on structure-activity relationships of distinct chemical modifications and relevant clinical trials.

PERSPECTIVE

ASOs are promising in cardiovascular drug innovation. We hope that future studies of lncRNA-based therapies would overcome existing technical limitations and help people who suffer from autophagy-involved CVDs.

摘要

背景

心血管疾病（CVDs）仍然是全球范围内的主要死亡原因。目前 CVD 治疗中的精准医学理念要求将个体遗传和环境变异性纳入其中，以实现疾病预防的个体化和治疗方案的个体化。自噬是一种进化上保守的细胞内降解过程，已被证明在各种 CVD 的发病机制中至关重要。然而，目前尚无针对自噬相关 CVD 的有效治疗方法。长链非编码 RNA（lncRNAs）是一类非编码 RNA 序列，在自噬调控中发挥多种作用，但关于 lncRNAs 与自噬相关 CVD 之间的关系仍有许多需要探索的地方。

总结

越来越多的证据表明，lncRNAs 在 CVD 背景下对调节自噬有重要作用。在这篇综述中，我们首先总结了 lncRNAs 在心血管自噬和自噬相关 CVD 中的作用的现有知识。然后，讨论了专门针对 lncRNAs 的反义寡核苷酸（ASO）在靶向调节病变心脏和血管中的自噬方面的最新进展，主要侧重于不同化学修饰的结构-活性关系和相关临床试验。