Bonauer Angelika, Carmona Guillaume, Iwasaki Masayoshi, Mione Marina, Koyanagi Masamichi, Fischer Ariane, Burchfield Jana, Fox Henrik, Doebele Carmen, Ohtani Kisho, Chavakis Emmanouil, Potente Michael, Tjwa Marc, Urbich Carmen, Zeiher Andreas M, Dimmeler Stefanie
Institute for Cardiovascular Regeneration, Centre of Molecular Medicine, Goethe-University Frankfurt, 60590 Frankfurt, Germany.
Science. 2009 Jun 26;324(5935):1710-3. doi: 10.1126/science.1174381. Epub 2009 May 21.
MicroRNAs (miRs) are small noncoding RNAs that regulate gene expression by binding to target messenger RNAs (mRNAs), leading to translational repression or degradation. Here, we show that the miR-17approximately92 cluster is highly expressed in human endothelial cells and that miR-92a, a component of this cluster, controls the growth of new blood vessels (angiogenesis). Forced overexpression of miR-92a in endothelial cells blocked angiogenesis in vitro and in vivo. In mouse models of limb ischemia and myocardial infarction, systemic administration of an antagomir designed to inhibit miR-92a led to enhanced blood vessel growth and functional recovery of damaged tissue. MiR-92a appears to target mRNAs corresponding to several proangiogenic proteins, including the integrin subunit alpha5. Thus, miR-92a may serve as a valuable therapeutic target in the setting of ischemic disease.
微小RNA（miR）是一类小的非编码RNA，通过与靶信使RNA（mRNA）结合来调控基因表达，从而导致翻译抑制或降解。在此，我们表明miR-17~92簇在人内皮细胞中高度表达，且该簇的一个组分miR-92a控制新血管生成（血管生成）。在内皮细胞中强制过表达miR-92a可在体外和体内阻断血管生成。在肢体缺血和心肌梗死的小鼠模型中，全身给予一种设计用于抑制miR-92a的拮抗剂可导致血管生长增强以及受损组织的功能恢复。miR-92a似乎靶向对应于几种促血管生成蛋白的mRNA，包括整合素亚基α5。因此，miR-92a可能是缺血性疾病治疗中的一个有价值的靶点。
