Stanford University, Department of Medicine, Stanford, CA 94305 , USA.
Expert Opin Ther Targets. 2013 May;17(5):557-64. doi: 10.1517/14728222.2013.765863. Epub 2013 Feb 2.
MicroRNAs (miRNAs) are small noncoding RNAs that not only regulate gene expression during normal development but can also be active players in several diseases. To date, several studies have demonstrated a possible role for specific miRNAs in the regulation of pulmonary vascular homeostasis suggesting that novel therapeutic agents which target these modulators of gene expression could serve to treat pulmonary arterial hypertension (PAH).
The characterization of miRNA-mediated gene modulation in the pulmonary circulation is expanding very rapidly. This review summarizes current relevant findings on the role of miRNAs in the pathogenesis of PAH and expands on the potential use of agents that target these molecules as future disease-modifying therapies.
Further understanding of miRNA biology and function in the pulmonary circulation will serve to further enhance our understanding of their contribution to the pathogenesis of PAH. The implementation of a systems biology approach will help accelerate the discovery of miRNAs that influence angiogenesis and cellular responses to vascular injury. Experimental characterization of these miRNAs using in vitro and in vivo methods will be required to validate the biological roles of these miRNAs prior to the consideration of their use as therapeutic targets in future clinical trials.
微小 RNA(miRNAs)是一类小型非编码 RNA,它们不仅在正常发育过程中调节基因表达,而且在几种疾病中也可以作为活跃的参与者。迄今为止,已有多项研究表明特定 miRNAs 在肺血管稳态调节中的可能作用,这表明靶向这些基因表达调节剂的新型治疗药物可能有助于治疗肺动脉高压(PAH)。
miRNA 介导的肺循环基因调节的特征正在迅速扩展。本综述总结了目前关于 miRNAs 在 PAH 发病机制中的作用的相关发现,并扩展了靶向这些分子的药物作为未来疾病修饰治疗的潜在用途。
进一步了解 miRNA 在肺循环中的生物学和功能将有助于进一步增强我们对其在 PAH 发病机制中作用的理解。系统生物学方法的实施将有助于加速发现影响血管生成和细胞对血管损伤反应的 miRNAs。需要使用体外和体内方法对这些 miRNAs 进行实验表征,以验证这些 miRNAs 的生物学作用,然后再考虑将其作为未来临床试验中的治疗靶点。