2月22日的《转化医学》（Science Translational Medicine）杂志发表了斯坦福大学研究人员的成果。研究发现，尼古丁可以促进腹主动脉瘤的发展，而microRNA-21可以阻断其发展。

在血管医学中，鉴定和治疗腹主动脉瘤（AAA,abdominal aortic aneurysm）仍然是一件相当困难的事情。抽烟被认为是腹主动脉瘤发生的主要原因。MicroRNA在心血管疾病中发挥重要调节作用，或许可以作为抑制腹主动脉瘤扩张的治疗靶点。

在两种腹主动脉瘤小鼠模型中，研究者鉴别出microRNA-21，它是血管壁平滑肌细胞增殖或凋亡的关键调节子。制作腹主动脉瘤模型的方法是注射猪胰弹性蛋白酶或灌注血管紧张肽II。随着腹主动脉瘤的发生，miR-21的表达也上升。

使用慢病毒载体过表达miR-21，可促进主动脉壁的细胞增殖，抑制其凋亡，这样可以阻止腹主动脉瘤的发展。MiR-21过表达显著降低了磷酸酶和张力蛋白同源蛋白的表达，导致AKT的磷酸化和激活，磷酸化的AKT可促进增殖、抑制凋亡。

研究结果表明，miR-21可作为腹主动脉瘤和其他血管病的治疗靶标。

MicroRNA-21 Blocks Abdominal Aortic Aneurysm Development and Nicotine-Augmented Expansion

Lars Maegdefessel, Junya Azuma, Ryuji Toh, Alicia Deng, Denis R. Merk, Azad Raiesdana, Nicholas J. Leeper, Uwe Raaz, Anke M. Schoelmerich, Michael V. McConnel, Ronald L. Dalman, Joshua M. Spin1 and Philip S. Tsao

Identification and treatment of abdominal aortic aneurysm (AAA) remains among the most prominent challenges in vascular medicine. MicroRNAs are crucial regulators of cardiovascular pathology and represent possible targets for the inhibition of AAA expansion. We identified microRNA-21 (miR-21) as a key modulator of proliferation and apoptosis of vascular wall smooth muscle cells during development of AAA in two established murine models. In both models (AAA induced by porcine pancreatic elastase or infusion of angiotensin II), miR-21 expression increased as AAA developed. Lentiviral overexpression of miR-21 induced cell proliferation and decreased apoptosis in the aortic wall, with protective effects on aneurysm expansion. miR-21 overexpression substantially decreased expression of the phosphatase and tensin homolog (PTEN) protein, leading to increased phosphorylation and activation of AKT, a component of a pro-proliferative and antiapoptotic pathway. Systemic injection of a locked nucleic acid–modified antagomir targeting miR-21 diminished the pro-proliferative impact of down-regulated PTEN, leading to a marked increase in the size of AAA. Similar results were seen in mice with AAA augmented by nicotine and in human aortic tissue samples from patients undergoing surgical repair of AAA (with more pronounced effects observed in smokers). Modulation of miR-21 expression shows potential as a new therapeutic option to limit AAA expansion and vascular disease progression.