Anti-hypertrophy effect of atorvastatin on myocardium depends on AMPK activation-induced miR-143-3p suppression via Foxo1.
Anti-hypertrophy effect of atorvastatin on myocardium depends on AMPK activation-induced miR-143-3p suppression via Foxo1.
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阿托伐他汀对心肌的抗肥厚作用取决于 AMPK 激活通过 Foxo1 诱导的 miR-143-3p 抑制。
DOI：
10.1016/j.biopha.2018.07.064
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发表时间：
2018-10
影响因子：
7.5
通讯作者：
Ping Yang
中科院分区：
文献类型：
--
作者：
Bo Yu;Dongna Liu;Hongli Zhang;Di Xie;Wei Nie;Kaiyao Shi;Ping Yang
左心室肥厚(LVH)是不同心脏疾病的共同病理特征。阿托伐他汀被用作降血脂药物，其心脏保护作用也是最近报道的。因此，本研究试图验证阿托伐他汀的抗肥厚作用及其相关机制。采用大鼠横断主动脉缩窄法(TAC)和血管紧张素II(Ang II)诱导心肌细胞肥大。然后用阿托伐他汀处理动物和细胞，评估其对心脏重量和结构以及细胞存活率、表面积和细胞凋亡率的影响。从AMPK/Foxo1/miR-143-3p轴进一步探讨阿托伐他汀抗肥厚作用的机制。结果表明，阿托伐他汀显着抑制TAC诱导的大鼠心脏重量增加，减轻心脏结构的恶化。在体外实验中，阿托伐他汀提高了血管紧张素转换酶II处理的H9c2细胞的存活率，减少了细胞表面积，减少了细胞凋亡率。在分子水平上，阿托伐他汀激活AMPK，进一步促进Foxo1激活，抑制miR-143-3p水平。将血管紧张素转换酶II处理的H9c2细胞与化合物C共同孵育，阻断阿托伐他汀对H9c2细胞的促存活和抗肥大作用，进一步证实了AMPK在阿托伐他汀治疗H9c2细胞过程中的关键作用。本研究结果证实了阿托伐他汀的抗心肌肥厚作用，并对阿托伐他汀的作用机制作了初步解释：阿托伐他汀抗心肌肥厚的作用依赖于通过AMPK和Foxo1激活抑制miR-143-3p。
Left ventricular hypertrophy (LVH) is a pathological characteristic shared by distinct heart disorders. Atorvastatin is employed as a lipid lowering agent and its heart protection effect has been recently reported as well. Thus, the current study attempted to validate the anti-hypertrophy effect of atorvastatin as well as the associated mechanism. Hypertrophic feature was induced in rats using transverse aortic constriction (TAC) method and in cardiomyocytes using angiotensin II (Ang II). Then the animals and cells were treated with atorvastatin and the effect on cardiac weight and structure as well as cell viability, surface area, and apoptosis was assessed. The mechanism associated with the anti-hypertrophy effect of atorvastatin was further explored by focusing on the AMPK/Foxo1/miR-143-3p axis. The results showed that the administration of atorvastatin significantly suppressed TAC-induced heart weight increase and attenuated cardiac structure deteriorations in rats. In in vitro assays, atorvastatin increased cell viability, and reduced cell surface area and apoptosis in Ang II-treated H9c2 cells. At molecular level, atorvastatin activated AMPK, which further promoted Foxo1 activation and suppressed miR-143-3p level. The key role of AMPK during atorvastatin treatment was further validated by subjecting Ang II-treated H9c2 cells to co-incubation of atorvastatin and Compound C, which blocked the pro-survival and anti-hypertrophy effect of atorvastatin on H9c2 cells. The findings outlined in the current study confirmed the anti-hypertrophy effect of atorvastatin and provided a preliminary explanation on the mechanism associated with the treatment: the protective effect of atorvastatin on myocardium against hypertrophy depended on miR-143-3p inhibition via AMPK and Foxo1 activation.
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影响因子：
3.7
作者：
Reichert K;Pereira do Carmo HR;Galluce Torina A;Diógenes de Carvalho D;Carvalho Sposito A;de Souza Vilarinho KA;da Mota Silveira-Filho L;Martins de Oliveira PP;Petrucci O
通讯作者：
Petrucci O
影响因子：
3.2
作者：
K. Ray;C. Cannon
通讯作者：
K. Ray;C. Cannon
DOI：
10.1016/s0734-3299(08)70393-9
发表时间：
2007
期刊：
Yearbook of Critical Care Medicine
影响因子：
--
作者：
J. Provencio
通讯作者：
J. Provencio
影响因子：
5
作者：
H. Hasegawa;R. Yamamoto;H. Takano;M. Mizukami;M. Asakawa;T. Nagai;I. Komuro
通讯作者：
H. Hasegawa;R. Yamamoto;H. Takano;M. Mizukami;M. Asakawa;T. Nagai;I. Komuro
影响因子：
37.8
作者：
Patel, R;Nagueh, SF;Marian, AJ
通讯作者：
Marian, AJ