An Endocrine Genetic Signal Between Blood Cells and Vascular Smooth Muscle Cells: Role of MicroRNA-223 in Smooth Muscle Function and Atherogenesis.
An Endocrine Genetic Signal Between Blood Cells and Vascular Smooth Muscle Cells: Role of MicroRNA-223 in Smooth Muscle Function and Atherogenesis.
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血细胞和血管平滑肌细胞之间的内分泌遗传信号：MicroRNA-223 在平滑肌功能和动脉粥样硬化形成中的作用。
DOI：
10.1016/j.jacc.2015.03.570
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发表时间：
2015-06-16
影响因子：
24
通讯作者：
Zhang, Chunxiang
中科院分区：
文献类型：
--
作者：
Shan, Zhen;Qin, Shanshan;Li, Wen;Wu, Weibin;Yang, Jian;Chu, Maoping;Li, Xiaokun;Huo, Yuqing;Schaer, Gary L.;Wang, Shenming;Zhang, Chunxiang
microRNA-223（miR-223）是造血谱系细胞特异性microRNA。然而，在血管平滑肌细胞（VSMC）和血管壁中已经鉴定出大量的miR-223，这些细胞不应该具有内源性miR-223。本研究旨在确定正常和动脉粥样硬化动脉中miR-223的来源以及miR-223在动脉粥样硬化形成中的作用。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的miR-223分泌以及miR-223进入VSMC和血管壁的能力。研究了miR-223水平对动脉粥样硬化动物和患者血清和动脉的后续变化和影响。血细胞能够将miR-223分泌到血清中。来自血细胞的microRNA-223是血液中最丰富的无细胞miRNA。血细胞分泌的miR-223可进入VSMCs和血管壁，通过靶基因产生较强的生物学效应。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miR-223水平显著升高。miR-223基因敲除可加重载脂蛋白E基因敲除小鼠的动脉粥样硬化病变。使用miR-223敲除小鼠验证miR-223对动脉粥样硬化形成的作用。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形成中发挥重要作用。miR-223作为一种介于血细胞和血管细胞之间的新型内分泌遗传信号，可能为动脉粥样硬化的发生提供新的机制和新的治疗靶点。
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.
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影响因子：
3.7
作者：
Rangrez AY;M'Baya-Moutoula E;Metzinger-Le Meuth V;Hénaut L;Djelouat MS;Benchitrit J;Massy ZA;Metzinger L
通讯作者：
Metzinger L
DOI：
10.1165/ajrcmb.26.1.4618
发表时间：
2002-01-01
影响因子：
6.4
作者：
Singer, M;Lefort, J;Vargaftig, BB
通讯作者：
Vargaftig, BB
DOI：
10.1161/atvbaha.109.188839
发表时间：
2009-07
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Wang H;Zhang W;Zhu C;Bucher C;Blazar BR;Zhang C;Chen JF;Linden J;Wu C;Huo Y
通讯作者：
Huo Y
影响因子：
16.6
作者：
Tabet, Fatiha;Vickers, Kasey C.;Torres, Luisa F. Cuesta;Wiese, Carrie B.;Shoucri, Bassem M.;Lambert, Gilles;Catherinet, Claire;Prado-Lourenco, Leonel;Levin, Michael G.;Thacker, Seth;Sethupathy, Praveen;Barter, Philip J.;Remaley, Alan T.;Rye, Kerry-Anne
通讯作者：
Rye, Kerry-Anne
影响因子：
5
作者：
Liu X;Cheng Y;Yang J;Xu L;Zhang C
通讯作者：
Zhang C