Dysregulation of angiogenesis-related microRNAs in endothelial progenitor cells from patients with coronary artery disease
Dysregulation of angiogenesis-related microRNAs in endothelial progenitor cells from patients with coronary artery disease
复制标题
DOI：
10.1016/j.bbrc.2010.12.119
复制
发表时间：
2011-02-04
影响因子：
3.1
通讯作者：
Kutryk, Michael J.
中科院分区：
文献类型：
--
作者：
Zhang, Qiuwang;Kandic, Ivana;Kutryk, Michael J.
内皮祖细胞（EPC）通过再内皮化和新生血管形成在血管修复和维持血管稳态中发挥重要作用。导致冠状动脉疾病 (CAD) 的心血管危险因素已被证明会对 EPC 产生负面影响，但其机制尚不清楚。在转录后水平负调控基因表达的 MicroRNA (miRNA) 已被证明会影响内皮细胞 (EC) 的血管生成作用，但人们对其在调节 EPC 功能中的作用知之甚少。在这项研究中，我们首先研究了 EPC 是否表达 EC 特异性、血管生成相关的 miRNA；然后确定与健康对照相比，CAD 患者的 EPC 中这些 miRNA 的表达是否发生改变。此外，我们还检查了已知可增加循环 EPC 数量的阿托伐他汀是否对 EPC miRNA 表达有影响。我们发现 EPC 产生 miR-126、miR-130a、miR-221、miR-222 和 miR-92a，迄今为止它们已被确定为最重要的血管生成 miRNA。在 CAD 患者的 EPC 中检测到这些 miRNA 的失调，并且阿托伐他汀治疗选择性地影响了 EPC 中 miRNA 的表达。我们的数据提供了证据，表明血管生成 miRNA 可能在 EPC 功能的控制中发挥重要作用，并且它们的失调可能导致冠状动脉疾病患者的 EPC 功能障碍。这些发现可能会导致预防和治疗 CAD 的新治疗方式的开发。 (c) 2011 Elsevier Inc. 保留所有权利。
Endothelial progenitor cells (EPCs) play an important role in vascular repair and maintenance of vascular homeostasis through re-endothelialization and neovascularization. Cardiovascular risk factors that contribute to coronary artery disease (CAD) have been shown to negatively impact EPCs, although the mechanisms are poorly understood. MicroRNAs (miRNAs) which negatively regulate gene expression at the post-transcriptional level have been shown to impact endothelial cell (EC) angiogenic actions, but little is known about their role in modulating EPC function. In this study we first investigated if EPCs expressed EC specific, angiogenesis-related miRNAs; then determined whether the expression of these miRNAs was altered in EPCs from CAD patients as compared with healthy controls. Furthermore, we examined if atorvastatin, known to increase circulating EPC numbers, had any effect on EPC miRNA expression. We found EPCs produced miR-126, miR-130a, miR-221, miR-222 and miR-92a which have thus far been identified as the most important angiogenic miRNAs. Dysregulation of these miRNAs was detected in EPCs from CAD patients and atorvastatin treatment selectively impacted miRNA expression in EPCs.Our data provide evidence that angiogenic miRNAs might play an important role in the control of EPC function, and that their dysregulaticin might contribute to EPC dysfunction in patients suffering from coronary artery disease. These findings might lead to the development of novel therapeutic modalities for the prevention and treatment of CAD. (c) 2011 Elsevier Inc. All rights reserved.