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ナガサカ ヤスコ
NAGASAKA Yasuko
長坂 安子 所属 医学部 医学科（東京女子医科大学病院） 職種 教授・基幹分野長 |
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| 論文種別 | 原著 |
| 言語種別 | 英語 |
| 査読の有無 | 査読あり |
| 表題 | Functional brown adipose tissue limits cardiomyocyte injury and adverse remodeling in catecholamine-induced cardiomyopathy. |
| 掲載誌名 | 正式名：Journal of molecular and cellular cardiology 略 称：J Mol Cell Cardiol ISSNコード：10958584/00222828 |
| 掲載区分 | 国外 |
| 巻・号・頁 | 84,pp.202-11 |
| 国際共著 | 国際共著 |
| 著者・共著者 | Thoonen Robrecht, Ernande Laura, Cheng Juan, Nagasaka Yasuko, Yao Vincent, Miranda-Bezerra Alexandre, Chen Chan, Chao Wei, Panagia Marcello, Sosnovik David E, Puppala Dheeraj, Armoundas Antonis A, Hindle Allyson, Bloch Kenneth D, Buys Emmanuel S, Scherrer-Crosbie Marielle |
| 発行年月 | 2015/07 |
| 概要 | Brown adipose tissue (BAT) has well recognized thermogenic properties mediated by uncoupling protein 1 (UCP1); more recently, BAT has been demonstrated to modulate cardiovascular risk factors. To investigate whether BAT also affects myocardial injury and remodeling, UCP1-deficient (UCP1(-/-)) mice, which have dysfunctional BAT, were subjected to catecholamine-induced cardiomyopathy. At baseline, there were no differences in echocardiographic parameters, plasma cardiac troponin I (cTnI) or myocardial fibrosis between wild-type (WT) and UCP1(-/-) mice. Isoproterenol infusion increased cTnI and myocardial fibrosis and induced left ventricular (LV) hypertrophy in both WT and UCP1(-/-) mice. UCP1(-/-) mice also demonstrated exaggerated myocardial injury, fibrosis, and adverse remodeling, as well as decreased survival. Transplantation of WT BAT to UCP1(-/-) mice prevented the isoproterenol-induced cTnI increase and improved survival, whereas UCP1(-/-) BAT transplanted to either UCP1(-/-) or WT mice had no effect on cTnI release. After 3 days of isoproterenol treatment, phosphorylated AKT and ERK were lower in the LV's of UCP1(-/-) mice than in those of WT mice. Activation of BAT was also noted in a model of chronic ischemic cardiomyopathy, and was correlated to LV dysfunction. Deficiency in UCP1, and accompanying BAT dysfunction, increases cardiomyocyte injury and adverse LV remodeling, and decreases survival in a mouse model of catecholamine-induced cardiomyopathy. Myocardial injury and decreased survival are rescued by transplantation of functional BAT to UCP1(-/-) mice, suggesting a systemic cardioprotective role of functional BAT. BAT is also activated in chronic ischemic cardiomyopathy. |
| DOI | 10.1016/j.yjmcc.2015.05.002 |
| PMID | 25968336 |