Dataset Information

Exosomes Derived From Epigallocatechin Gallate-Treated Cardiomyocytes Attenuated Acute Myocardial Infarction by Modulating MicroRNA-30a.

ABSTRACT: Background:Ischemia-derived exosomes can restrict excessive autophagy by transferring microRNA-30a (miR30a) to cells. Reports have confirmed that epigallocatechin gallate (EGCG) alleviates acute myocardial infarction (AMI) by regulating autophagy; however, research evaluating the communication with cardiomyocytes and exosomes is lacking. This study aimed to explore whether exosomes derived from EGCG-treated cardiomyocytes mitigated AMI by adjusting miR30a to inactivate apoptosis and autophagy. Methods:Exosomes were extracted from cardiomyocytes, cultured either in control or AMI condition, with or without EGCG pretreatment. The exosome characteristics were analyzed by nanoparticle tracking analyses and transmission electron microscopy. The change in miR30a in cells and exosomes was demonstrated by qRT-PCR. H9c2 or stable miR30a knockdown (miR30aKD) cell lines were incubated with exosomes derived from EGCG-treated cardiomyocytes in vitro or in vivo. The effect of EGCG and exosomes on I/R-induced cardiomyocyte apoptosis and autophagy was assessed. Results:EGCG improved the activity of cardiomyocytes, and increased average diameter, concentration, miR30a mRNA level, and specific protein expression in AMI-derived exosomes produced by cardiomyocytes. Moreover, the coincubation of AMI cells with EGCG or exosomes derived from EGCG-treated cardiomyocytes attenuated cardiomyocyte apoptosis and autophagy. Conclusions:The findings showed that EGCG upregulates miR30a, which was efficiently transferred via exosomes between cardiomyocytes, thereby contributing to the suppression of apoptosis and autophagy. By focusing on the cardiomyocyte microenvironment, we identified a new target of EGCG alleviating AMI by regulating apoptosis and autophagy.

SUBMITTER: Zhang C

PROVIDER: S-EPMC7054242 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Exosomes Derived From Epigallocatechin Gallate-Treated Cardiomyocytes Attenuated Acute Myocardial Infarction by Modulating MicroRNA-30a.

Zhang Chan C Gan Xiaowen X Liang Ronggan R Jian Jie J

Frontiers in pharmacology 20200226

<h4>Background</h4>Ischemia-derived exosomes can restrict excessive autophagy by transferring microRNA-30a (miR30a) to cells. Reports have confirmed that epigallocatechin gallate (EGCG) alleviates acute myocardial infarction (AMI) by regulating autophagy; however, research evaluating the communication with cardiomyocytes and exosomes is lacking. This study aimed to explore whether exosomes derived from EGCG-treated cardiomyocytes mitigated AMI by adjusting miR30a to inactivate apoptosis and auto ...[more]

PMID: 32161548

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Project description:ObjectiveIndividuals who experience myocardial infarction (MI) often experience anxiety. Green tea has potent antioxidative properties and, epigallocatechin-3-gallate (EGCG), which is a primary component of tea polyphenols, has advantageous effects on anxiety and depression. However, its mechanism of action regarding the inhibition of anxiety-like symptoms after MI remains unclear. This study examined whether EGCG alleviated anxiety-like behavior in MI rats and its possible mechanism.Material and methodsRats were administered a daily gavage of EGCG (50 mg/kg) 7 days before and 14 consecutive days after the MI procedure. The open-field test and light/dark shuttle box were performed to evaluate anxiety-like behavior. Serum and hippocampus interleukin (IL)-6 levels were tested using ELISA. Caspase 3, caspase 8, caspase 9 and bcl-2 messenger RNA levels in the hippocampus were determined using quantitative polymerase chain reaction, and STAT3 protein was detected by Western blot.ResultsResults of the open field test and light/dark shuttle box task demonstrated that the MI procedure induced anxiety-like behavior in the animals, and this impairment was improved by EGCG. Daily EGCG administration significantly decreased the level of IL-6 both in serum and hippocampus after MI. The administration of EGCG also significantly moderated the expression of caspases 3, 8, and 9 mRNA, which was related to apoptosis in the hippocampus. Furthermore, EGCG also downregulated the expression of STAT3, which was related to the activity of IL-6. These results suggest that EGCG alleviated anxiety-like behavior by inhibiting increases in neuroinflammation and apoptosis in the rat hippocampus. In addition, EGCG reversed alterations of IL-6 and STAT3 in the brain to alleviate apoptosis in the hippocampus.ConclusionsThus, EGCG reversed anxiety-like behavior through an anti-inflammation effect to alleviate apoptosis in neurons and may be a useful therapeutic material for anxiety-like behavior after MI.

Project description:The imbalance between the synthesis of reactive oxygen species and their elimination by antioxidant defense systems results in macromolecular damage and disruption of cellular redox signaling, affecting cardiac structure and function, thus contributing to contractile dysfunction, myocardial hypertrophy, and fibrosis in chronic heart failure [chronic heart failure (CHF)]. The Kelch-like ECH-associated protein 1-nuclear factor erythroid 2-related factor 2 (Nrf2) pathway is an important antioxidant defense mechanism and is closely associated with oxidative stress-mediated cardiac remodeling in CHF. In the present study, we investigated the regulation of myocardial Nrf2 in the postmyocardial infarction (post-MI) state. Six weeks post-MI, Nrf2 protein was downregulated in the heart, resulting in a decrease of Nrf2-targeted antioxidant enzymes, whereas paradoxically the transcription of Nrf2 was increased, suggesting that translational inhibition of Nrf2 may contribute to the dysregulation in CHF. We therefore hypothesized that microRNAs may be involved in the translational repression of Nrf2 mRNA in the setting of CHF. Using quantitative real-time PCR analysis, we found that three microRNAs, including microRNA-27a, microRNA-28-3p, and microRNA-34a, were highly expressed in the left ventricle of infarcted hearts compared with other organs. Furthermore, in vitro analysis revealed that cultured cardiac myocytes and fibroblasts expressed these three microRNAs in response to TNF-? stimulation. These microRNAs were preferentially incorporated into exosomes and secreted into the extracellular space in which microRNA-enriched exosomes mediated intercellular communication and Nrf2 dysregulation. Taken together, these results suggest that increased local microRNAs induced by MI may contribute to oxidative stress by the inhibition of Nrf2 translation in CHF. NEW & NOTEWORTHY The results of this work provide a novel mechanism mediated by microRNA-enriched exosomes, contributing to the nuclear factor erythroid 2-related factor 2 dysregulation and subsequent oxidative stress. Importantly, these new findings will provide a promising strategy to improve the therapeutic efficacy through targeting nuclear factor erythroid 2-related factor 2-related microRNAs in the chronic heart failure state, which show potentially clinical applications.

Dataset Information

Exosomes Derived From Epigallocatechin Gallate-Treated Cardiomyocytes Attenuated Acute Myocardial Infarction by Modulating MicroRNA-30a.

Publications

Exosomes Derived From Epigallocatechin Gallate-Treated Cardiomyocytes Attenuated Acute Myocardial Infarction by Modulating MicroRNA-30a.

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