美国科研人员发现了一种可调节血管生长的“开关”——微型核糖核酸分子miR－132，并且找到了控制该“开关”的方法。这一研究成果有望对癌症和心脑血管疾病的治疗产生积极影响。
这项研究由美国加州大学圣迭戈分校医学院和密歇根大学癌症中心的研究人员共同完成。研究小组在英国《自然·医学》杂志网络版上报告说，他们发现在正常血管形成或再生期间，形成血管内壁的内皮细胞会暴露在一种具有“开关”功效的物质环境中，导致血管开始扩张、生长。通过分析，研究人员确定这个“开关”就是微型核糖核酸分子miR－132。
负责此项研究的病理学家戴维·切雷什说，血管与这个“开关”的关系好比是汽车与油门、刹车片之间的关系。在肿瘤的血管里，miR－132分子非常丰富，它具有保障血管广泛生长的能力，结果造成病变部位的血管像油门轰响、刹车失灵的汽车一样在人体组织内闯荡。
切雷什说，根据这一原理，科研人员制作出了遏制miR－132分子的物质和miR－132分子补充物。在对患有癌症和视网膜疾病的老鼠进行实验时，研究者发现，遏制miR－132分子的物质能使老鼠病变部位的血管生长受到抑制，阻止病情进一步发展。对于miR－132分子补充物的效果，研究者暂时没有提供详细资料。
但他们认为，对于心脑血管疾病患者和因其他疾病血管受损者来说，miR－132分子补充物可能有助于调节其血管生长，缓解病情。
目前，切雷什和同事正在设计一种纳米粒，以期将遏制miR－132分子的物质和miR－132分子补充物准确输送到老鼠的病变部位，并且降低这两种物质的毒副作用(高原)。（生物谷Bioon.com）
生物谷近期特别推荐会议：
2010细胞治疗研究进展与临床前沿研讨会 www.Cell-therapies.net 2010年9月23日-25日天津召开
第一届肿瘤基础和转化医学国际研讨会 www.cancerasia.org 2010年10月12日-10月15日上海召开
生物谷推荐原文出处：
Nature Medicine doi:10.1038/nm.2186
MicroRNA-132–mediated loss of p120RasGAP activates the endothelium to facilitate pathological angiogenesis
Sudarshan Anand1, Bharat K Majeti1, Lisette M Acevedo1, Eric A Murphy1, Rajesh Mukthavaram1, Lea Scheppke1, Miller Huang1, David J Shields1, Jeffrey N Lindquist1, Philip E Lapinski2, Philip D King2, Sara M Weis1 & David A Cheresh1
Although it is well established that tumors initiate an angiogenic switch, the molecular basis of this process remains incompletely understood. Here we show that the miRNA miR-132 acts as an angiogenic switch by targeting p120RasGAP in the endothelium and thereby inducing neovascularization. We identified miR-132 as a highly upregulated miRNA in a human embryonic stem cell model of vasculogenesis and found that miR-132 was highly expressed in the endothelium of human tumors and hemangiomas but was undetectable in normal endothelium. Ectopic expression of miR-132 in endothelial cells in vitro increased their proliferation and tube-forming capacity, whereas intraocular injection of an antagomir targeting miR-132, anti–miR-132, reduced postnatal retinal vascular development in mice. Among the top-ranking predicted targets of miR-132 was p120RasGAP, which we found to be expressed in normal but not tumor endothelium. Endothelial expression of miR-132 suppressed p120RasGAP expression and increased Ras activity, whereas a miRNA-resistant version of p120RasGAP reversed the vascular response induced by miR-132. Notably, administration of anti–miR-132 inhibited angiogenesis in wild-type mice but not in mice with an inducible deletion of Rasa1 (encoding p120RasGAP). Finally, vessel-targeted nanoparticle delivery1 of anti–miR-132 restored p120RasGAP expression in the tumor endothelium, suppressed angiogenesis and decreased tumor burden in an orthotopic xenograft mouse model of human breast carcinoma. We conclude that miR-132 acts as an angiogenic switch by suppressing endothelial p120RasGAP expression, leading to Ras activation and the induction of neovascularization, whereas the application of anti–miR-132 inhibits neovascularization by maintaining vessels in the resting state.
