Ozaki Kouichi, Inoue Katsumi, Sato Hiroshi, Iida Aritoshi, Ohnishi Yozo, Sekine Akihiro, Sato Hideyuki, Odashiro Keita, Nobuyoshi Masakiyo, Hori Masatsugu, Nakamura Yusuke, Tanaka Toshihiro
Laboratory for Cardiovascular Diseases, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Tokyo 108-8639, Japan.
Nature. 2004 May 6;429(6987):72-5. doi: 10.1038/nature02502.
Myocardial infarction (MI) has become one of the leading causes of death in the world. Its pathogenesis includes chronic formation of plaque inside the vessel wall of the coronary artery and acute rupture of the artery, implicating a number of inflammation-mediating molecules, such as the cytokine lymphotoxin-alpha (LTA). Functional variations in LTA are associated with susceptibility to MI. Here we show that LTA protein binds to galectin-2, a member of the galactose-binding lectin family. Our case-control association study in a Japanese population showed that a single nucleotide polymorphism in LGALS2 encoding galectin-2 is significantly associated with susceptibility to MI. This genetic substitution affects the transcriptional level of galectin-2 in vitro, potentially leading to altered secretion of LTA, which would then affect the degree of inflammation; however, its relevance to other populations remains to be clarified. Smooth muscle cells and macrophages in the human atherosclerotic lesions expressed both galectin-2 and LTA. Our findings thus suggest a link between the LTA cascade and the pathogenesis of MI.
心肌梗死（MI）已成为全球主要死因之一。其发病机制包括冠状动脉血管壁内斑块的慢性形成和动脉的急性破裂，涉及多种炎症介导分子，如细胞因子淋巴毒素-α（LTA）。LTA的功能变异与MI易感性相关。在此我们表明，LTA蛋白与半乳糖凝集素-2结合，半乳糖凝集素-2是半乳糖结合凝集素家族的一员。我们在日本人群中进行的病例对照关联研究表明，编码半乳糖凝集素-2的LGALS2中的一个单核苷酸多态性与MI易感性显著相关。这种基因替代在体外影响半乳糖凝集素-2的转录水平，可能导致LTA分泌改变，进而影响炎症程度；然而，其与其他人群的相关性仍有待阐明。人类动脉粥样硬化病变中的平滑肌细胞和巨噬细胞同时表达半乳糖凝集素-2和LTA。因此，我们的研究结果提示LTA级联反应与MI发病机制之间存在联系。
