Tissue- and plasma-specific MicroRNA signatures for atherosclerotic abdominal aortic aneurysm.
Tissue- and plasma-specific MicroRNA signatures for atherosclerotic abdominal aortic aneurysm.
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DOI：
10.1161/jaha.112.000745
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发表时间：
2012-10
影响因子：
5.4
通讯作者：
Sawa Y
中科院分区：
文献类型：
--
作者：
Kin K;Miyagawa S;Fukushima S;Shirakawa Y;Torikai K;Shimamura K;Daimon T;Kawahara Y;Kuratani T;Sawa Y
动脉粥样硬化性腹主动脉瘤（AAA）是一种进行性、渐进性的主动脉破裂，在没有手术干预的情况下会导致死亡。调节AAA发生和进展的关键因素尚不清楚，因此难以进行针对性干预。microRNA在动脉粥样硬化中起着重要作用，动脉粥样硬化性冠状动脉疾病的特征在于组织和血浆特异性microRNA特征。然而，很少有人知道microRNA参与AAA病理。本研究检测了与AAA特异性相关的组织和血浆microRNA。分别从接受AAA修复术（n=13;平均年龄，68±6岁）和主动脉瓣置换术（n=7;平均年龄，66±4岁）的患者中采集AAA和正常壁组织样本。通过高通量microRNA阵列评估microRNA表达，并通过实时聚合酶链反应验证在初始筛选中显示显着表达差异的单个microRNA。与纤维化（miR-29 b）、炎症（miR-124 a、miR-146 a、miR-155和miR-223）和内皮（miR-126、let-7家族成员和miR-21）相关的microRNA在AAA组织中显著上调。单核细胞趋化蛋白-1与miR-124 a、-146 a和-223;肿瘤坏死因子-α与miR-126和-223;转化生长因子-β与miR-146 a的表达水平呈显著负相关。与健康对照组（n=12;平均年龄，51±11岁）和冠状动脉疾病患者（n=17;平均年龄，71±9岁）相比，AAA患者（n=23;平均年龄，72±9岁）血浆中AAA组织中上调的microRNA（如miR-29 b、miR-124 a、miR-155和miR-223）表达显著降低。一些microRNA的表达在AAA组织中特异性上调，从而促进了对microRNA在AAA发病机制中的功能以及使用microRNA生物标志物进行AAA诊断的可能性的进一步研究。
Atherosclerotic abdominal aortic aneurysm (AAA) is a progressive, gradual aortic rupture that results in death in the absence of surgical intervention. Key factors that regulate initiation and progression of AAA are unknown, making targeted interventions difficult. MicroRNAs play a fundamental role in atherosclerosis, and atherosclerotic coronary artery disease is characterized by tissue- and plasma-specific microRNA signatures. However, little is known about microRNAs involved in AAA pathology. This study examined tissue and plasma microRNAs specifically associated with AAA. AAA and normal wall tissues were sampled from patients undergoing AAA repair (n=13; mean age, 68±6 years) and aortic valve replacement surgery (n=7; mean age, 66±4 years), respectively. MicroRNA expression was assessed by high-throughput microRNA arrays and validated by real-time polymerase chain reaction for individual microRNAs that showed significant expression differences in the initial screening. MicroRNAs related to fibrosis (miR-29b), inflammation (miR-124a, miR-146a, miR-155, and miR-223), and endothelium (miR-126, let-7 family members, and miR-21) were significantly upregulated in AAA tissue. Significant negative correlations were seen in expression levels of monocyte chemoattractant protein-1 and miR-124a, -146a, and -223; tumor necrosis factor-α and miR-126 and -223; and transforming growth factor-β and miR-146a. Expression of microRNAs, such as miR-29b, miR-124a, miR-155, and miR-223, that were upregulated in AAA tissue was significantly reduced in plasma of patients with AAA (n=23; mean age, 72±9 years) compared to healthy controls (n=12; mean age, 51±11 years) and patients with coronary artery disease (n=17; mean age, 71±9 years). The expression of some microRNAs was specifically upregulated in AAA tissue, warranting further studies on the microRNA function in AAA pathogenesis and on the possibility of using a microRNA biomarker for AAA diagnosis.