Divergent and Overlapping Roles for Selected Phytochemicals in the Regulation of Pathological Cardiac Hypertrophy.
Divergent and Overlapping Roles for Selected Phytochemicals in the Regulation of Pathological Cardiac Hypertrophy.
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DOI：
10.3390/molecules26051210
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发表时间：
2021-02-24
期刊：
影响因子：
--
通讯作者：
Ferguson BS
中科院分区：
文献类型：
--
作者：
Evans L;Shen Y;Bender A;Burnett LE;Li M;Habibian JS;Zhou T;Ferguson BS
植物性食品，如水果、蔬菜、全谷物、豆类、坚果、种子和其他食品，被认为对心脏有益。这些植物性食品中的化学物质，即植物化学物质，被认为可以保护心脏。然而，植物化学物质预防病理性心脏肥大等临床终点的机制仍在阐明中。我们试图描述 18 种选定的植物化学物质预防去氧肾上腺素和佛波醇 12-肉豆蔻酸酯 13-乙酸酯介导的心肌细胞增大的重叠和不同机制的特征。在测试的 18 种化合物中，有 6 种可减弱 PE 和 PMA 介导的新生大鼠心室肌细胞的增大。细胞活力测定表明芹菜素、黄芩素、盐酸小檗碱、大黄素、木犀草素和槲皮素二水合物不会通过细胞毒性减小细胞大小。六种植物化学物质中的四种，芹菜素、黄芩素、盐酸小檗碱和大黄素，可有效抑制应激诱导的肥大，并针对细胞内信号传导和全基因组 mRNA 表达变化进行了进一步分析。四种植物化学物质对丝裂原激活蛋白激酶和蛋白激酶 D 的调节存在差异。RNA 测序进一步显示基因调节的差异，而通路分析表明炎症通路调节的重叠。综上所述，这项研究提供了对心脏保护植物化学物质的全面分析。这些数据强调了两个明确的观察结果：（1）这些化合物主要针对心肌细胞内不同的基因途径；（2）重叠信号传导和基因途径的调节可能对于这些植物化学物质的抗肥厚作用特别重要。尽管有这些新发现，未来仍需要研究啮齿动物心力衰竭模型，以了解这些化合物在心脏中的作用。
Plant-based foods, like fruits, vegetables, whole grains, legumes, nuts, seeds and other foodstuffs, have been deemed as heart healthy. The chemicals within these plant-based foods, i.e., phytochemicals, are credited with protecting the heart. However, the mechanistic actions of phytochemicals, which prevent clinical endpoints, such as pathological cardiac hypertrophy, are still being elucidated. We sought to characterize the overlapping and divergent mechanisms by which 18 selected phytochemicals prevent phenylephrine- and phorbol 12-myristate 13-acetate-mediated cardiomyocyte enlargement. Of the tested 18 compounds, six attenuated PE- and PMA-mediated enlargement of neonatal rat ventricular myocytes. Cell viability assays showed that apigenin, baicalein, berberine hydrochloride, emodin, luteolin and quercetin dihydrate did not reduce cell size through cytotoxicity. Four of the six phytochemicals, apigenin, baicalein, berberine hydrochloride and emodin, robustly inhibited stress-induced hypertrophy and were analyzed further against intracellular signaling and genome-wide changes in mRNA expression. The four phytochemicals differentially regulated mitogen-activated protein kinases and protein kinase D. RNA-sequencing further showed divergence in gene regulation, while pathway analysis demonstrated overlap in the regulation of inflammatory pathways. Combined, this study provided a comprehensive analysis of cardioprotective phytochemicals. These data highlight two defining observations: (1) that these compounds predominantly target divergent gene pathways within cardiac myocytes and (2) that regulation of overlapping signaling and gene pathways may be of particular importance for the anti-hypertrophic actions of these phytochemicals. Despite these new findings, future works investigating rodent models of heart failure are still needed to understand the roles for these compounds in the heart.
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影响因子：
5.6
作者：
García-Conesa MT;Chambers K;Combet E;Pinto P;Garcia-Aloy M;Andrés-Lacueva C;de Pascual-Teresa S;Mena P;Konic Ristic A;Hollands WJ;Kroon PA;Rodríguez-Mateos A;Istas G;Kontogiorgis CA;Rai DK;Gibney ER;Morand C;Espín JC;González-Sarrías A
通讯作者：
González-Sarrías A
影响因子：
2.5
作者：
Al-Shafei, Ahmad I. M.;El-Gendy, Ola A. A.
通讯作者：
El-Gendy, Ola A. A.
影响因子：
5.7
作者：
Chen, Huai-Min;Liou, Shu-Fen;Yeh, Jwu-Lai
通讯作者：
Yeh, Jwu-Lai
影响因子：
7.1
作者：
Janssen, PLTMK;Mensink, RP;Katan, MB
通讯作者：
Katan, MB
影响因子：
5.3
作者：
Harrison, Brooke C.;Kim, Mi-Sung;McKinsey, Timothy A.
通讯作者：
McKinsey, Timothy A.