CD73 regulates vascular smooth muscle cell functions and facilitates atherosclerotic plaque formation
CD73 regulates vascular smooth muscle cell functions and facilitates atherosclerotic plaque formation
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DOI：
10.1002/iub.1448
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发表时间：
2015-11
期刊：
影响因子：
4.6
通讯作者：
Jiayin Yang;Rongrong Jian;Jiangang Yu;Xiuling Zhi;Xiaohong Liao;Jerry Yu;P. Zhou
中科院分区：
文献类型：
--
作者：
Jiayin Yang;Rongrong Jian;Jiangang Yu;Xiuling Zhi;Xiaohong Liao;Jerry Yu;P. Zhou
细胞外腺苷（adenosine）是由胞外5′-核苷酸酶（CD 73）通过酶催化产生的，它被发现可促进动脉粥样硬化（AS）的发生。因此，抑制CD 73可以减弱AS。本研究旨在探讨CD 73在AS发生发展过程中的作用，并进一步探讨其在平滑肌细胞中的细胞和分子机制。在小鼠颈动脉结扎模型中，CD 73的失活抑制了血管平滑肌细胞的迁移和增殖。在体外实验中，CD 73的RNA干扰抑制人脐动脉平滑肌细胞的迁移、增殖和泡沫细胞转化。此外，我们使用喂食西方饮食16周的Apoe-/-小鼠建立了动脉粥样硬化模型。ApoE−/−小鼠中CD 73减弱的AS和高脂血症的灭活。总之，我们的数据表明，CD 73通过促进血管平滑肌细胞的迁移、增殖和泡沫细胞转化以及升高血脂水平来促进AS。因此，抑制CD 73可能有利于预防和治疗AS。© 2015 IUBMB Life，67（11）：853-860，2015
Extracellular adenosine, generated by ecto‐5′‐nucleotidase (CD73) via enzymatic catalyzation, has been found to facilitate atherosclerosis (AS). Thus, suppressing CD73 may attenuate AS. In this study, we evaluated the role of CD73 during AS development and further explored cellular and molecular mechanism in smooth muscle cells (SMCs). In a mouse model of carotid artery ligation, inactivation of CD73 inhibited migration and proliferation of vascular SMCs. In in vitro experiments, RNA interference of CD73 inhibited migration, proliferation, and foam cell transformation of human umbilical artery smooth muscle cells. Further, we established an atherosclerotic model using ApoE−/− mice fed with a western diet for 16 weeks. Inactivation of CD73‐attenuated AS and hyperlipidemia in ApoE−/− mice. In conclusion, our data suggest that CD73 facilitates AS by promoting migration, proliferation, and foam cell transformation of vascular SMCs and elevating serum lipid levels. Thus, inhibition of CD73 may be beneficial for prevention and treatment of AS. © 2015 IUBMB Life, 67(11):853–860, 2015