Wronska Anetta
Department of Physiology and Cellular Biophysics, Clyde and Helen Wu Center for Molecular Cardiology, Columbia University Vagelos College of Physicians and Surgeons, New York, New York
J Pharmacol Exp Ther. 2023 Jan;384(1):123-132. doi: 10.1124/jpet.121.001152. Epub 2022 Jul 2.
Since their discovery in 1993, microRNAs (miRNAs) have emerged as important regulators of many crucial cellular processes, and their dysregulation have been shown to contribute to multiple pathologic conditions, including cardiovascular disease (CVD). miRNAs have been found to regulate the expression of various genes involved in cardiac development and function and in the development and progression of CVD. Many miRNAs are master regulators fine-tuning the expression of multiple, often interrelated, genes involved in inflammation, apoptosis, fibrosis, senescence, and other processes crucial for the development of different forms of CVD. This article presents a review of recent developments in our understanding of the role of miRNAs in the development of CVD and surveys their potential applicability as therapeutic targets and biomarkers to facilitate CVD diagnosis, prognosis, and treatment. There are currently multiple potential miRNA-based therapeutic agents in different stages of development, which can be grouped into two classes: miRNA mimics (replicating the sequence and activity of their corresponding miRNAs) and antagomiRs (antisense inhibitors of specific miRNAs). However, in spite of promising preliminary data and our ever-increasing knowledge about the mechanisms of action of specific miRNAs, miRNA-based therapeutics and biomarkers have yet to be approved for clinical applications. SIGNIFICANCE STATEMENT: Over the last few years microRNAs have emerged as crucial, specific regulators of the cardiovascular system and in the development of cardiovascular disease, by posttranscriptional regulation of their target genes. The minireview presents the most recent developments in this area of research, including the progress in diagnostic and therapeutic applications of microRNAs. microRNAs seem very promising candidates for biomarkers and therapeutic agents, although some challenges, such as efficient delivery and unwanted effects, need to be resolved.
自1993年被发现以来,微小RNA(miRNA)已成为许多关键细胞过程的重要调节因子,其失调已被证明与多种病理状况有关,包括心血管疾病(CVD)。人们发现miRNA可调节参与心脏发育和功能以及CVD发生和发展的各种基因的表达。许多miRNA是主要调节因子,可微调参与炎症、凋亡、纤维化、衰老以及对不同形式CVD发展至关重要的其他过程的多个(通常相互关联的)基因的表达。本文综述了我们对miRNA在CVD发生中作用的最新认识进展,并探讨了它们作为治疗靶点和生物标志物在促进CVD诊断、预后和治疗方面的潜在适用性。目前有多种基于miRNA的治疗药物处于不同的研发阶段,可分为两类:miRNA模拟物(复制其相应miRNA的序列和活性)和抗miR(特定miRNA的反义抑制剂)。然而,尽管有令人鼓舞的初步数据以及我们对特定miRNA作用机制的了解不断增加,但基于miRNA的治疗方法和生物标志物尚未获批用于临床应用。意义声明:在过去几年中,微小RNA已通过对其靶基因的转录后调控,成为心血管系统和心血管疾病发生发展的关键、特异性调节因子。本综述介绍了该研究领域的最新进展,包括微小RNA在诊断和治疗应用方面的进展。微小RNA似乎是非常有前景的生物标志物和治疗药物候选物,尽管一些挑战,如有效递送和不良影响,需要得到解决。
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