Functional brown adipose tissue limits cardiomyocyte injury and adverse remodeling in catecholamine-induced cardiomyopathy.
Functional brown adipose tissue limits cardiomyocyte injury and adverse remodeling in catecholamine-induced cardiomyopathy.
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DOI：
10.1016/j.yjmcc.2015.05.002
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发表时间：
2015-07
影响因子：
5
通讯作者：
Scherrer-Crosbie, Marielle
中科院分区：
文献类型：
--
作者：
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
棕色脂肪组织（BAT）具有公认的由解偶联蛋白1（UCP 1）介导的产热特性;最近，BAT已被证明可调节心血管危险因素。为了研究BAT是否也影响心肌损伤和重塑，UCP 1缺陷（UCP 1 −/−）小鼠，具有功能失调的BAT，受到儿茶酚胺诱导的心肌病。在基线时，野生型（WT）和UCP 1 −/−小鼠之间的超声心动图参数、血浆心肌肌钙蛋白I（cTnI）或心肌纤维化无差异。在WT和UCP 1 −/−小鼠中，输注异丙肾上腺素可增加cTnI和心肌纤维化，并诱导左心室（LV）肥大。UCP 1 −/−小鼠也表现出过度的心肌损伤、纤维化和不良重塑，以及存活率降低。将WT BAT移植到UCP 1 −/−小鼠中可防止异丙肾上腺素诱导的cTnI增加并改善存活率，而将UCP 1 −/− BAT移植到UCP 1 −/−或WT小鼠中对cTnI释放没有影响。异丙肾上腺素治疗3天后，UCP 1 −/−小鼠LV中磷酸化AKT和ERK低于WT小鼠。在慢性缺血性心肌病模型中也观察到BAT的激活，并与LV功能障碍相关。UCP 1缺乏和伴随的BAT功能障碍增加了心肌细胞损伤和不利的LV重构，并降低了小鼠模型中的存活率。通过将功能性BAT移植到UCP 1 −/−小鼠中，挽救了心肌损伤和存活率下降，这表明功能性BAT具有全身心脏保护作用。BAT在慢性缺血性心肌病中也被激活。
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.
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DOI：
10.1152/ajpheart.01236.2006
发表时间：
2007-07-01
影响因子：
4.8
作者：
Buys, Emmanuel S.;Raher, Michael J.;Scherrer-Crosbie, Marielle
通讯作者：
Scherrer-Crosbie, Marielle
DOI：
10.1152/ajpregu.00021.2009
发表时间：
2010-11-01
影响因子：
2.8
作者：
Meyer, Carola W.;Willershaeuser, Monja;Klingenspor, Martin
通讯作者：
Klingenspor, Martin
影响因子：
64.8
作者：
Enerback, S;Jacobsson, A;Kozak, LP
通讯作者：
Kozak, LP
Labdane 二萜可防止心肌细胞缺氧/再灌注损伤：参与 AKT 激活。
影响因子：
9
作者：
通讯作者：
--
影响因子：
3.7
作者：
Montalvo C;Villar AV;Merino D;García R;Ares M;Llano M;Cobo M;Hurlé MA;Nistal JF
通讯作者：
Nistal JF