Epigallocatechin-3-gallate exerts cardioprotective effects related to energy metabolism in pressure overload-induced cardiac dysfunction
Epigallocatechin-3-gallate exerts cardioprotective effects related to energy metabolism in pressure overload-induced cardiac dysfunction
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DOI：
10.1016/j.abb.2022.109217
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发表时间：
2022-04-25
影响因子：
3.9
通讯作者：
Tian, Jie
中科院分区：
文献类型：
--
作者：
Mou, Qiuhong;Jia, Zhongli;Tian, Jie
背景资料：探讨表没食子儿茶素没食子酸酯（EGCG）对压力超负荷性心功能不全的保护作用及其机制。研究方法：采用腹主动脉缩窄术（abdominal aortic constriction，AAC）建立慢性心力衰竭模型，随机分为假手术组、AAC组、AAC + EGCG组。超声心动图和组织切片染色分别评估心脏功能和病理学。实时定量聚合酶链反应检测基因表达水平。采用无标记定量蛋白质组学技术对心脏全蛋白质组进行研究，并对差异表达蛋白进行生物信息学分析。Western blot检测差异蛋白的表达水平和可靠性。结果：与AAC组相比，AAC + EGCG组经EGCG治疗后收缩功能明显改善。EGCG可抑制AAC后心肌纤维化和心肌肥大，沿着降低心钠素、B型利钠肽、1型和3型胶原α 1和转化生长因子β 1。定量蛋白质组学共鉴定出162个差异表达蛋白，其中18个与心血管疾病密切相关。生物信息学分析表明，EGCG主要通过改变氧化磷酸化和脂质代谢等能量代谢过程发挥治疗作用。此外，NADH：线粒体呼吸链的重要组成部分泛醌氧化还原酶亚基S4在AAC后增加，然后被EGCG逆转，这与蛋白质组学结果一致。结论：表没食子儿茶素没食子酸酯（EGCG）可能通过增强能量代谢来纠正心力衰竭后心脏收缩功能障碍和防止心脏重构，这为我们研究EGCG在压力超负荷性心功能障碍中的心脏保护作用提供了新的思路。
Background: To investigate the mechanisms of potential cardioprotective effects of epigallocatechin-3-gallate (EGCG) in pressure overload-induced cardiac dysfunction. Methods: A chronic heart failure model was established using abdominal aortic constriction (AAC) surgery, rats were divided into sham, AAC, and AAC + EGCG groups. Echocardiography and tissue section staining were performed to evaluate cardiac function and pathology, respectively. Gene expression level were detected with quantitative real-time polymerase chain reactions. Label-free quantitative proteomics was used to investigate the whole proteomes of heart, and the differentially expressed proteins were analyzed using bioinformatics methods. Western blot was performed to validate the levels and the reliability of the differential proteins. Results: Compared with the AAC group, systolic dysfunction was improved in AAC + EGCG group after EGCG treatment. EGCG inhibited myocardial fibrosis and cardiac hypertrophy after AAC, along with reducing atrial natriuretic protein, B-type natriuretic peptide, collagen types 1 and 3 alpha 1, and transforming growth factor beta-1. Quantitative proteomics identified a total of 162 differentially expressed proteins, among them, 18 were closely related to cardiovascular disorders. Bioinformatics analyses showed that EGCG played a therapeutic role mainly by changing energy metabolism processes, such as oxidative phosphorylation and lipid metabolism. Furthermore, NADH: ubiquinone oxidoreductase subunit S4, an important component of the mitochondrial respiratory chain, was increased after AAC and then reversed by EGCG, which was consistent with the proteomics results. Conclusions: EGCG may correct cardiac systolic dysfunction and prevent cardiac remodeling after heart failure via enhancing the energy metabolism, which provides us with new insights into cardioprotective effects of EGCG related to the energy metabolisms in pressure overload-induced cardiac dysfunction.