ジュウジョウ　ケンタロウ   JUJO Kentaro   重城　健太郎    所属   埼玉医科大学  医学部 総合医療センター　心臓内科    職種   教授
論文種別	学術雑誌(原著)
言語種別	英語
査読の有無	査読あり
表題	CXCR4 blockade augments bone marrow progenitor cell recruitment to the neovasculature and reduces mortality after myocardial infarction
掲載誌名	正式名：PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA ISSNコード：00278424
出版社	NATL ACAD SCIENCES
巻・号・頁	107(24),11008-11013頁
著者・共著者	Kentaro Jujo,Hiromichi Hamada,Atsushi Iwakura,Tina Thorne,Haruki Sekiguchi,Trevor Clarke,Aiko Ito,Sol Misener,Toshikazu Tanaka,Ekaterina Klyachko,Koichi Kobayashi,Joern Tongers,Jerome Roncalli,Yukio Tsurumi,Nobuhisa Hagiwara,Douglas W. Losordo
発行年月	2010/06
概要	We hypothesized that a small molecule CXCR4 antagonist, AMD3100 (AMD), could augment the mobilization of bone marrow (BM)-derived endothelial progenitor cells (EPCs), thereby enhancing neovascularization and functional recovery after myocardial infarction. Single-dose AMD injection administered after the onset of myocardial infarction increased circulating EPC counts and myocardial vascularity, reduced fibrosis, and improved cardiac function and survival. In mice transplanted with traceable BM cells, AMD increased BM-derived cell incorporation in the ischemic border zone. In contrast, continuous infusion of AMD, although increasing EPCs in the circulation, worsened outcome by blocking EPC incorporation. In addition to its effects as a CXCR4 antagonist, AMD also up-regulated VEGF and matrix metalloproteinase 9 (MMP-9) expression, and the benefits of AMD were not observed in the absence of MMP-9 expression in the BM. These findings suggest that AMD3100 preserves cardiac function after myocardial infarction by enhancing BM-EPC-mediated neovascularization, and that these benefits require MMP-9 expression in the BM, but not in the ischemic region. Our results indicate that AMD3100 could
DOI	10.1073/pnas.0914248107