Crocetin protects against cardiac hypertrophy by blocking MEK-ERK1/2 signalling pathway |
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Authors: | Jun Cai Fang-Fang Yi Zhou-Yan Bian Di-Fei Shen Long Yang Ling Yan Qi-Zhu Tang Xin-Chun Yang Hongliang Li |
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Institution: | Cardiovascular Research Center, Massachusetts General Hospital, and Harvard Medical School, Boston, MA, USA;Department of Cardiology, Beijing Chaoyang Hospital, Affiliate of Capital Medical University, Beijing, China;Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China;Cardiovascular Research Institute of Wuhan University, Wuhan, China |
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Abstract: | 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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Keywords: | crocetin reactive oxygen species cardiac remodelling fibrosis NF-κB ERK1/2 |
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