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	Reduction in Hexokinase II Levels Results in Decreased Cardiac Function and Altered Remodeling After Ischemia/Reperfusion Injury
掲載誌名	正式名：CIRCULATION RESEARCH ISSNコード：00097330
出版社	LIPPINCOTT WILLIAMS&WILKINS
巻・号・頁	108(1),60-U128頁
著者・共著者	Rongxue Wu,Kirsten M. Smeele,Eugene Wyatt,Yoshihiko Ichikawa,Otto Eerbeek,Lin Sun,Kusum Chawla,Markus W. Hollmann,Varun Nagpal,Sami Heikkinen,Markku Laakso,Kentaro Jujo,J. Andrew Wasserstrom,Coert J. Zuurbier,Hossein Ardehali
発行年月	2011/01
概要	Rationale: Cardiomyocytes switch substrate utilization from fatty acid to glucose under ischemic conditions; however, it is unknown how perturbations in glycolytic enzymes affect cardiac response to ischemia/reperfusion (I/R). Hexokinase (HK)II is a HK isoform that is expressed in the heart and can bind to the mitochondrial outer membrane.Objective: We sought to define how HKII and its binding to mitochondria play a role in cardiac response and remodeling after I/R.Methods and Results: We first showed that HKII levels and its binding to mitochondria are reduced 2 days after I/R. We then subjected the hearts of wild-type and heterozygote HKII knockout (HKII(+/-)) mice to I/R by coronary ligation. At baseline, HKII(+/-) mice have normal cardiac function; however, they display lower systolic function after I/R compared to wild-type animals. The mechanism appears to be through an increase in cardiomyocyte death and fibrosis and a reduction in angiogenesis; the latter is through a decrease in hypoxia-inducible factor-dependent pathway signaling in cardiomyocytes. HKII mitochondrial binding is also critical for cardiomyocyte survival, because its displacement in tissue culture with a s
DOI	10.1161/CIRCRESAHA.110.223115