Cardiovascular Center, University Hospital Zurich, Zurich, Switzerland.
Cardiovasc Res. 2012 Mar 15;93(4):614-22. doi: 10.1093/cvr/cvr311. Epub 2011 Dec 1.
MicroRNAs (miRNAs), small non-coding RNAs, play a critical role in differentiation and self-renewal of pluripotent stem cells, as well as in differentiation of cardiovascular lineage cells. Several miRNAs have been demonstrated to repress stemness factors such as Oct4, Nanog, Sox2 and Klf4 in embryonic stem cells, thereby promoting embryonic stem cell differentiation. Furthermore, targeting of different miRNAs promotes reprogramming towards induced pluripotent stem cells. MicroRNAs are critical for vascular smooth muscle cell differentiation and phenotype regulation, and miR-143 and miR-145 play a particularly important role in this respect. Notably, these miRNAs are down-regulated in several cardiovascular disease states, such as in atherosclerotic lesions and vascular neointima formation. MicroRNAs are critical regulators of endothelial cell differentiation and ischaemia-induced neovascularization. miR-126 is important for vascular integrity, endothelial cell proliferation and neovascularization. miR-1 and miR-133 are highly expressed in cardiomyocytes and their precursors and regulate cardiomyogenesis. In addition, miR-499 promotes differentiation of cardiomyocyte progenitor cells. Notably, miRNA expression is altered in cardiovascular disease states, and recent studies suggest that dysregulated miRNAs may limit cardiovascular repair responses. Dysregulation of miRNAs may lead to an altered function and differentiation of cardiovascular progenitor cells, which is also likely to represent a limitation of autologous cell-based treatment approaches in these patients. These findings suggest that targeting of specific miRNAs may represent an interesting novel opportunity to impact on endogenous cardiovascular repair responses, including effects on stem/progenitor cell differentiation and functions. This approach may also serve to optimize cell-based treatment approaches in patients with cardiovascular disease.
微小 RNA（miRNAs）是一类小型非编码 RNA，在多能干细胞的分化和自我更新以及心血管谱系细胞的分化中发挥着关键作用。已经证实，几种 miRNAs 可以抑制胚胎干细胞中的干性因子，如 Oct4、Nanog、Sox2 和 Klf4，从而促进胚胎干细胞的分化。此外，不同 miRNAs 的靶向作用可以促进向诱导多能干细胞的重编程。miRNAs 对于血管平滑肌细胞的分化和表型调节至关重要，miR-143 和 miR-145 在这方面发挥着特别重要的作用。值得注意的是，这些 miRNAs 在几种心血管疾病状态中下调，如动脉粥样硬化病变和血管新生内膜形成。miRNAs 是内皮细胞分化和缺血诱导的血管新生的关键调节因子。miR-126 对于血管完整性、内皮细胞增殖和血管新生至关重要。miR-1 和 miR-133 在心肌细胞及其前体细胞中高度表达，并调节心肌发生。此外，miR-499 促进心肌细胞祖细胞的分化。值得注意的是，miRNA 的表达在心血管疾病状态中发生改变，最近的研究表明，失调的 miRNAs 可能限制心血管修复反应。miRNAs 的失调可能导致心血管祖细胞的功能和分化发生改变，这也可能代表了这些患者中自体细胞治疗方法的局限性。这些发现表明，针对特定 miRNAs 可能代表了一种有趣的新机会，可以影响内源性心血管修复反应，包括对干细胞/祖细胞分化和功能的影响。这种方法也可能有助于优化心血管疾病患者的细胞治疗方法。
