Murakami Kazuo
Department of Health Care and Preventive Medicine, Matsuyama Red Cross Hospital, 1 Bunkyo-cho, Matsuyama, Ehime, 790-8524, Japan.
Curr Hypertens Rev. 2015;11(2):80-90. doi: 10.2174/1573402111666150401105317.
Hypertension is a major risk factor of cardiovascular diseases and a most important health problem in developed countries. Investigations on pathophysiology of hypertension have been based on gene products from coding region that occupies only about 1% of total genome region. On the other hand, non-coding region that occupies almost 99% of human genome has been regarded as "junk" for a long time and went unnoticed until these days. But recently, it turned out that noncoding region is extensively transcribed to non-coding RNAs and has various functions. This review highlights recent updates on the significance of non-coding RNAs such as micro RNAs and long non-coding RNAs (lncRNAs) on the pathogenesis of hypertension, also providing an introduction to basic biology of noncoding RNAs. For example, microRNAs are associated with hypertension via neuro-fumoral factor, sympathetic nerve activity, ion transporters in kidneys, endothelial function, vascular smooth muscle phenotype transformation, or communication between cells. Although reports of lncRNAs on pathogenesis of hypertension are scarce at the moment, new lncRNAs in relation to hypertension are being discovered at a rapid pace owing to novel techniques such as microarray or next-generation sequencing. In the clinical settings, clinical use of non-coding RNAs in identifying cardiovascular risks or developing novel tools for treating hypertension such as molecular decoy or mimicks is promising, although improvement in chemical modification or drug delivery system is necessary.
高血压是心血管疾病的主要危险因素,也是发达国家最重要的健康问题。对高血压病理生理学的研究一直基于仅占基因组区域约1%的编码区基因产物。另一方面,几乎占人类基因组99%的非编码区长期以来一直被视为“垃圾”,直到最近才受到关注。但最近发现,非编码区广泛转录为非编码RNA并具有多种功能。本综述重点介绍了微小RNA和长链非编码RNA(lncRNA)等非编码RNA在高血压发病机制方面的最新进展,同时也介绍了非编码RNA的基础生物学知识。例如,微小RNA通过神经体液因子、交感神经活动、肾脏中的离子转运体、内皮功能、血管平滑肌表型转化或细胞间通讯与高血压相关。虽然目前关于lncRNA在高血压发病机制方面的报道较少,但由于微阵列或新一代测序等新技术,与高血压相关的新lncRNA正在迅速被发现。在临床环境中,非编码RNA在识别心血管风险或开发治疗高血压的新工具(如分子诱饵或模拟物)方面的临床应用前景广阔,尽管化学修饰或药物递送系统仍需改进。