ICS II protects against cardiac hypertrophy by regulating metabolic remodelling, not by inhibiting autophagy
ICS II protects against cardiac hypertrophy by regulating metabolic remodelling, not by inhibiting autophagy
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ICS II 通过调节代谢重塑而非抑制自噬来预防心脏肥大
DOI：
10.1111/jcmm.16175
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发表时间：
2020-12-08
影响因子：
5.3
通讯作者：
Shen D
中科院分区：
文献类型：
--
作者：
Han D;Wang B;Cui X;He W;zhang Y;Jiang Q;Wang F;Liu Z;Shen D
心肌肥大的特征在于代谢底物利用的转变。因此，酮体摄取和代谢的调节可能对诱导心脏重塑的心脏损伤具有有益作用。在这项研究中，我们研究了淫羊藿苷II（ICS II）是否可以防止小鼠和心肌细胞的心脏肥大。为了建立心脏肥大动物和细胞模型，小鼠经受横向主动脉缩窄（TAC），并且胚胎大鼠心肌细胞（H9 C2）用血管紧张素II（一种神经体液应激物）刺激。在体内和体外的结果表明，ICS II治疗改善压力超负荷诱导的心脏肥大和保存心脏功能。此外，细胞凋亡和氧化应激的ICS II的存在下减少。此外，ICS II抑制TAC诱导的心脏和血管紧张素II刺激的心肌细胞中的过度自噬。从机制上讲，我们发现ICS II给药可调节心脏重塑中SIRT 3的表达。SIRT 3激活增加了酮体的运输和利用。总的来说，我们的数据表明ICS II通过调节酮体和脂肪酸代谢来减轻心脏肥大，这可能是由于SIRT 3-AMPK通路的激活。ICS II治疗可能为改善心肌肥厚和心力衰竭的心肌代谢提供新的治疗策略。
Cardiac hypertrophy is characterized by a shift in metabolic substrate utilization. Therefore, the regulation of ketone body uptake and metabolism may have beneficial effects on heart injuries that induce cardiac remodelling. In this study, we investigated whether icariside II (ICS II) protects against cardiac hypertrophy in mice and cardiomyocytes. To create cardiac hypertrophy animal and cell models, mice were subjected to transverse aortic constriction (TAC), and embryonic rat cardiomyocytes (H9C2) were stimulated with angiotensin II, a neurohumoral stressor. Both the in vivo and in vitro results suggest that ICS II treatment ameliorated pressure overload–induced cardiac hypertrophy and preserved heart function. In addition, apoptosis and oxidative stress were reduced in the presence of ICS II. Moreover, ICS II inhibited excess autophagy in TAC‐induced hearts and angiotensin II–stimulated cardiomyocytes. Mechanistically, we found that ICS II administration regulated SIRT3 expression in cardiac remodelling. SIRT3 activation increased ketone body transportation and utilization. Collectively, our data show that ICS II attenuated cardiac hypertrophy by modulating ketone body and fatty acid metabolism, and that this was likely due to the activation of the SIRT3‐AMPK pathway. ICS II treatment may provide a new therapeutic strategy for improving myocardial metabolism in cardiac hypertrophy and heart failure.
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影响因子：
5
作者：
Schiattarella GG;Hill JA
通讯作者：
Hill JA
影响因子：
37.8
作者：
Lai YC;Tabima DM;Dube JJ;Hughan KS;Vanderpool RR;Goncharov DA;St Croix CM;Garcia-Ocaña A;Goncharova EA;Tofovic SP;Mora AL;Gladwin MT
通讯作者：
Gladwin MT
艾卡瑞苷 II 通过抑制胶原蛋白合成改善自发性高血压大鼠的心肌纤维化
影响因子：
3.3
作者：
Fu, Shu;Li, Yeli;Yang, Danli
通讯作者：
Yang, Danli
影响因子：
37.8
作者：
Nielsen, Roni;Moller, Niels;Wiggers, Henrik
通讯作者：
Wiggers, Henrik
影响因子：
5.6
作者：
Allard, MF
通讯作者：
Allard, MF