Experimental Vascular Medicine, Institute for Cardiovascular Prevention, Ludwig-Maximilians-University Munich, Pettenkoferstraße 9, 80336 Munich, Germany.
Cardiovasc Res. 2013 Jul 15;99(2):294-303. doi: 10.1093/cvr/cvt096. Epub 2013 Apr 23.
Changes in haemodynamic forces in the vascular system result in an altered expression of miRs, which play important gene-regulatory roles by pairing to the mRNAs of protein-coding genes to fine-tune post-transcriptional repression. The development and structure of blood vessels are highly adapted to haemodynamic forces, such as shear stress, cyclic stretch, and circumferential wall stress, generated by the conductance of blood. Thus, fluctuations in shear stress contribute to miR-regulated differential gene expression in endothelial cells (ECs), which is essential for maintenance of vascular physiology. Several microRNAs have been identified that are induced by high shear stress mediating an atheroprotective role, such as miR-10a, miR-19a, miR-23b, miR-101, and miR-143/145. While changes in the expression profile of miR-21 and miR-92a by high shear stress are associated with an atheroprotective function, low shear stress-induced expression of miR-21, miR-92a, and miR-663 results in a pathological EC phenotype. MiR-155 fulfils pleiotropic functions in different regions of vasculature, when exposed to different modes of shear stress. Thus, changes in shear stress result in differential expression of numerous miRs, triggering the balance between susceptibility and resistance to cardiovascular diseases. Further elucidating the regulation of miRs by flow may allow future clinical applications of miRs as diagnostic and therapeutic tools.
血管系统中血流动力的变化导致 miR 的表达发生改变，miR 通过与蛋白质编码基因的 mRNA 配对，发挥重要的基因调控作用，精细调节转录后抑制。血管的发育和结构高度适应血流产生的血流动力，如切应力、循环拉伸和周向壁应力。因此，切应力的波动有助于 miR 调节内皮细胞（EC）中的差异基因表达，这对于维持血管生理学至关重要。已经鉴定出几种受高切应力诱导的 microRNA，它们具有抗动脉粥样硬化作用，如 miR-10a、miR-19a、miR-23b、miR-101 和 miR-143/145。虽然高切应力引起的 miR-21 和 miR-92a 表达谱的变化与抗动脉粥样硬化功能有关，但低切应力诱导的 miR-21、miR-92a 和 miR-663 的表达导致病理 EC 表型。当暴露于不同的切应力模式时，miR-155 在血管的不同区域发挥多种功能。因此，切应力的变化导致众多 miR 的差异表达，触发了对心血管疾病易感性和抵抗力之间的平衡。进一步阐明 miR 受血流的调节可能为未来 miR 作为诊断和治疗工具的临床应用提供依据。
