Crocetin protects against cardiac hypertrophy by blocking MEK-ERK1/2 signalling pathway.
Crocetin protects against cardiac hypertrophy by blocking MEK-ERK1/2 signalling pathway.
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DOI：
10.1111/j.1582-4934.2008.00620.x
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发表时间：
2009-05
影响因子：
5.3
通讯作者：
Li H
中科院分区：
文献类型：
--
作者：
Cai J;Yi FF;Bian ZY;Shen DF;Yang L;Yan L;Tang QZ;Yang XC;Li H
氧化应激在病理性心脏肥大和心力衰竭的进展中起着关键作用。由于藏花酸在体外和体内抑制氧化应激，因此我们认为藏花酸可以通过靶向氧化应激依赖性信号传导来抑制心脏肥大。我们使用原代培养的心肌细胞和成纤维细胞以及一种成熟的心脏肥大动物模型测试了这一假设。结果表明，藏红花酸 (1–10 μM) 剂量依赖性地阻断体外血管生成素 II (Ang II; 1 μM) 诱导的心脏肥大。我们的数据进一步显示，通过心脏重量/体重和肺重量/体重比、超声心动图参数和肥厚标志物的基因表达进行评估，藏红花酸（50毫克/公斤/天）既可以预防并逆转主动脉束带（AB）引起的心脏肥大。藏红花酸对心脏肥大的抑制作用是通过阻断活性氧（ROS）依赖性丝裂原激活蛋白激酶（MAPK）/细胞外信号调节激酶-1/2（MEK/ERK1/2）途径和GATA结合蛋白4（GATA-4）激活来介导的。进一步的研究表明，藏花酸通过阻断核因子 kappa B (NF-κB) 信号传导来抑制炎症，并通过消除 MEK-ERK1/2 信号传导来减弱纤维化和胶原蛋白合成。总体而言，我们的结果表明，藏红花酸是一种潜在安全且廉价的临床疗法，通过抑制 ROS 依赖性信号通路，具有针对心脏肥大和纤维化的保护潜力。
Oxidative stress plays a critical role in the progression of pathological cardiac hypertrophy and heart failure. Because crocetin represses oxidative stress in vitro and in vivo, we have suggested that crocetin would repress cardiac hypertrophy by targeting oxidative stress-dependent signalling. We tested this hypothesis using primary cultured cardiac myocytes and fibroblasts and one well-established animal model of cardiac hypertrophy. The results showed that crocetin (1–10 μM) dose-dependently blocked cardiac hypertrophy induced by angiogensin II (Ang II; 1 μM) in vitro. Our data further revealed that crocetin (50 mg/kg/day) both prevented and reversed cardiac hypertrophy induced by aortic banding (AB), as assessed by heart weight/body weight and lung weight/body weight ratios, echocardio-graphic parameters and gene expression of hypertrophic markers. The inhibitory effect of crocetin on cardiac hypertrophy is mediated by blocking the reactive oxygen species (ROS)-dependent mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase-1/2 (MEK/ERK1/2) pathway and GATA binding protein 4 (GATA-4) activation. Further investigation demonstrated that crocetin inhibited inflammation by blocking nuclear factor kappa B (NF-κB) signalling and attenuated fibrosis and collagen synthesis by abrogating MEK-ERK1/2 signalling. Overall, our results indicate that crocetin, which is a potentially safe and inexpensive therapy for clinical use, has protective potential in targeting cardiac hypertrophy and fibrosis by suppression of ROS-dependent signalling pathways.
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影响因子：
3
作者：
Liehn, Elisa A.;Zernecke, Alma;Weber, Christian
通讯作者：
Weber, Christian
影响因子：
5.3
作者：
Neri M;Cerretani D;Fiaschi AI;Laghi PF;Lazzerini PE;Maffione AB;Micheli L;Bruni G;Nencini C;Giorgi G;D'Errico S;Fiore C;Pomara C;Riezzo I;Turillazzi E;Fineschi V
通讯作者：
Fineschi V
影响因子：
8.3
作者：
Li, Hong-Liang;She, Zhi-Gang;Liu, De-Pei
通讯作者：
Liu, De-Pei
影响因子：
15.9
作者：
Li, Hong-Liang;Liu, Chen;Liu, Peter P.
通讯作者：
Liu, Peter P.
DOI：
10.1097/mco.0b013e32830460c2
发表时间：
2008-07-01
影响因子：
3.1
作者：
Navab, Mohamad;Gharavi, Nima;Watson, Andrew D.
通讯作者：
Watson, Andrew D.