Shan Zhen, Qin Shanshan, Li Wen, Wu Weibin, Yang Jian, Chu Maoping, Li Xiaokun, Huo Yuqing, Schaer Gary L, Wang Shenming, Zhang Chunxiang
Rush University Cardiovascular Research Center and Department of Pharmacology, Rush University Medical Center, Chicago, Illinois.
Division of Vascular Surgery and the Laboratory of General Surgery, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
J Am Coll Cardiol. 2015 Jun 16;65(23):2526-37. doi: 10.1016/j.jacc.2015.03.570.
MicroRNA-223 (miR-223) is a hematopoietic lineage cell-specific microRNA. However, a significant amount of miR-223 has been identified in vascular smooth muscle cells (VSMCs) and vascular walls that should not have endogenous miR-223.
This study sought to determine the sources of miR-223 in normal and atherosclerotic arteries and the role of miR-223 in atherogenesis.
The levels and sources of miR-223 in blood cells (leukocytes and platelets), serum, blood microparticles, VSMCs, and vascular walls were determined. Both in vivo and in vitro studies were conducted to evaluate miR-223 secretion by blood cells and the ability of miR-223 to enter VSMCs and vascular walls. Subsequent changes in and the effects of miR-223 levels on serum and arteries in atherosclerotic animals and patients were investigated.
Blood cells were able to secrete miR-223 into serum. MicroRNA-223 from blood cells was the most abundant cell-free miRNA in blood. Blood cell-secreted miR-223 could enter VSMCs and vascular walls, which produced strong biological effects via its target genes. In both atherosclerotic apolipoprotein-E knockout mice and patients with atherosclerosis, miR-223 levels were significantly increased in serum and atherosclerotic vascular walls. The atherosclerotic lesions in apolipoprotein-E knockout mice were exacerbated by miR-223 knockdown. The effect of miR-223 on atherogenesis was verified using miR-223 knockout mice.
Blood cell-secreted miR-223 enters vascular cells and walls, and appears to play important roles in VSMC function and atherogenesis. As a novel endocrine genetic signal between blood cells and vascular cells, miR-223 may provide a novel mechanism and new therapeutic target for atherosclerosis.
微小RNA-223（miR-223）是一种造血谱系细胞特异性微小RNA。然而，在本不应有内源性miR-223的血管平滑肌细胞（VSMC）和血管壁中已鉴定出大量miR-223。
本研究旨在确定正常动脉和动脉粥样硬化动脉中miR-223的来源以及miR-223在动脉粥样硬化发生中的作用。
测定血细胞（白细胞和血小板）、血清、血液微粒、VSMC和血管壁中miR-223的水平和来源。进行体内和体外研究以评估血细胞分泌miR-223的情况以及miR-223进入VSMC和血管壁的能力。研究动脉粥样硬化动物和患者中miR-223水平对血清和动脉的后续变化及影响。
血细胞能够将miR-223分泌到血清中。来自血细胞的微小RNA-223是血液中最丰富的无细胞微小RNA。血细胞分泌的miR-223可进入VSMC和血管壁，并通过其靶基因产生强大的生物学效应。在动脉粥样硬化载脂蛋白E基因敲除小鼠和动脉粥样硬化患者中，血清和动脉粥样硬化血管壁中的miR-223水平均显著升高。miR-223敲低加剧了载脂蛋白E基因敲除小鼠的动脉粥样硬化病变。使用miR-223基因敲除小鼠验证了miR-223对动脉粥样硬化发生的影响。
血细胞分泌的miR-223进入血管细胞和血管壁，似乎在VSMC功能和动脉粥样硬化发生中起重要作用。作为血细胞与血管细胞之间的一种新型内分泌遗传信号，miR-223可能为动脉粥样硬化提供一种新机制和新的治疗靶点。
