Department of Vascular Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, PR China.
Tohoku J Exp Med. 2010 Nov;222(3):187-93. doi: 10.1620/tjem.222.187.
Abdominal aortic aneurysm (AAA) is a lethal disease, occurring mostly in men more than 65 years of age. Until recently, the pathogenesis of AAA remains poorly understood. MicroRNAs (miRNAs) are a novel class of endogenous small non-coding RNAs that play important roles in diverse biological and pathological processes including cardiovascular diseases. However, their biological roles in AAA formation have not been elucidated. In this study, we employed oligonucleotide microarrays to detect and compare miRNA expression profiles in a rat model of AAA. The abdominal aorta was exposed and incubated for 20 min with saline supplemented with calcium chloride and collagenase. After 28 days, the treated aortas were evaluated by digital measurement and angiography. A 50% increase over the normal diameter is considered as AAA. Our results revealed a set of differentially expressed miRNAs, with 10 significantly up-regulated and 5 significantly down-regulated miRNAs in AAA tissues. Four miRNAs (miR-19a, miR-19b, miR-132, and miR-221) were randomly selected for validation using real-time RT-PCR. Functional annotations of all putative targets of differentially expressed miRNAs via bioinformatics approaches revealed that predicted targets were highly enriched and involved in several key signaling pathways important for AAA formation, including pathways in cancer and signaling pathways involving mitogen-activated protein kinase, Wnt, neurotrophin, and ErbB. In summary, this study indicates that miRNAs might contribute to AAA formation probably by affecting multiple target genes and signaling pathways, which is expected to provide new clues to develop targeted therapies against this calamitous disease.
腹主动脉瘤（AAA）是一种致命的疾病，主要发生在 65 岁以上的男性中。直到最近，AAA 的发病机制仍知之甚少。microRNAs（miRNAs）是一类新的内源性小分子非编码 RNA，在包括心血管疾病在内的多种生物学和病理学过程中发挥重要作用。然而，它们在 AAA 形成中的生物学作用尚未阐明。在这项研究中，我们使用寡核苷酸微阵列检测和比较了 AAA 大鼠模型中的 miRNA 表达谱。将腹主动脉暴露并与氯化钙和胶原酶补充的生理盐水孵育 20 分钟。28 天后，通过数字测量和血管造影评估处理过的主动脉。正常直径增加 50%被认为是 AAA。我们的结果显示了一组差异表达的 miRNAs，其中 AAA 组织中有 10 个显著上调和 5 个显著下调的 miRNAs。随机选择 4 个 miRNAs（miR-19a、miR-19b、miR-132 和 miR-221）进行实时 RT-PCR 验证。通过生物信息学方法对差异表达 miRNA 的所有假定靶标进行功能注释表明，预测的靶标高度富集并涉及 AAA 形成的几个关键信号通路，包括癌症途径和涉及丝裂原活化蛋白激酶、Wnt、神经营养因子和 ErbB 的信号通路。总之，这项研究表明，miRNAs 可能通过影响多个靶基因和信号通路促进 AAA 的形成，这有望为开发针对这种灾难性疾病的靶向治疗提供新的线索。
