一项新研究的发现提示，从受损细胞释放的RNA是血液凝固的一种关键性辅因子。
德国Justus-Liebig大学的Klaus T. Preissner博士及其同事的这项新研究显示，细胞外RNA能够激活凝血因子XII和XI。这些发现被发表于4月10日的《美国科学院院刊》(Proc Natl Acad Sci USA 2007;104:6388-6393.)上。
在动脉血栓形成的小鼠模型中，作者发现RNA经常附着于富纤维蛋白的血栓上。使用RNA酶而不是DNA酶预处理，可减缓血栓增大。
作者总结说，来自受损或坏死细胞的细胞外RNA，特别是在病理或严重组织受损情况下，寻找天然“异物表面”，并为因子XII/XI诱导的接触活化/血液凝固扩增提供促凝辅因子模板。
部分英文原文：
Published online before print April 3, 2007
Proc. Natl. Acad. Sci. USA, 10.1073/pnas.0608647104
Medical Sciences
Extracellular RNA constitutes a natural procoagulant cofactor in blood coagulation
( contact phase activation | thrombosis | RNase | vascular injury | wound healing )
Christian Kannemeier * , Aya Shibamiya  , Fumie Nakazawa  ¶, Heidi Trusheim , Clemens Ruppert ||, Philipp Markart ||, Yutong Song , Eleni Tzima , Elisabeth Kennerknecht **, Michael Niepmann , Marie-Luise von Bruehl **, Daniel Sedding , Steffen Massberg **, Andreas Günther ||, Bernd Engelmann , and Klaus T. Preissner ,
*Research Laboratories, Aventis Behring, D-35392 Marburg, Germany; Departments of Biochemistry and ||Internal Medicine II, Medical School, Justus-Liebig-Universität, D-35002 Giessen, Germany; Graduate School of Health Sciences, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8519, Japan; **Deutsches Herzzentrum, Technische Universität, D-80636 Munich, Germany; and Institute of Clinical Chemistry, Ludwig-Maximilians-Universität, D-81377 Munich, Germany
Edited by Charles T. Esmon, Oklahoma Medical Research Foundation, Oklahoma City, OK, and approved February 20, 2007 (received for review October 8, 2006)
Upon vascular injury, locally controlled haemostasis prevents life-threatening blood loss and ensures wound healing. Intracellular material derived from damaged cells at these sites will become exposed to blood components and could contribute to blood coagulation and pathological thrombus formation. So far, the functional and mechanistic consequences of this concept are not understood. Here, we present in vivo and in vitro evidence that different forms of eukaryotic and prokaryotic RNA serve as promoters of blood coagulation. Extracellular RNA was found to augment (auto-)activation of proteases of the contact phase pathway of blood coagulation such as factors XII and XI, both exhibiting strong RNA binding. Moreover, administration of exogenous RNA provoked a significant procoagulant response in rabbits. In mice that underwent an arterial thrombosis model, extracellular RNA was found associated with fibrin-rich thrombi, and pretreatment with RNase (but not DNase) significantly delayed occlusive thrombus formation. Thus, extracellular RNA derived from damaged or necrotic cells particularly under pathological conditions or severe tissue damage represents the long sought natural "foreign surface" and provides a procoagulant cofactor template for the factors XII/XI-induced contact activation/amplification of blood coagulation. Extracellular RNA thereby reveals a yet unrecognized target for antithrombotic intervention, using RNase or related therapeutic strategies.
英文全文链接：www.pnas.org/cgi/content/full/0608647104/DC1
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