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Hyperbaric oxygen-induced long non-coding RNA MALAT1 exosomes suppress MicroRNA-92a expression in a rat model of acute myocardial infarction.

ABSTRACT: Hyperbaric oxygen (HBO) improves angiogenesis. The effect of HBO on metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a pro-angiogenic long non-coding RNA, in cardiac myocyte-derived exosomes and acute myocardial infarction (AMI) is unknown. We aimed to investigate whether MALAT1 is altered in cardiac myocyte-derived exosomes in response to HBO as well as the molecular regulatory mechanisms of MALAT1 in cardiac myocytes treated with HBO. Cardiac myocytes were cultured, and HBO was applied at 2.5 atmosphere absolute in a hyperbaric chamber. Exosomes were extracted from the culture media. A rat model of AMI generated by the ligation of the left anterior descending artery was used. HBO significantly increased MALAT1 expression in cardiac myocytes and HBO-induced MALAT1 and exosomes attenuated miR-92a expression after myocardial infarction. Expression of krüppel-like factor 2 (KLF2) and CD31 was significantly decreased after infarction and HBO-induced exosomes significantly reversed the expression. Silencing of MALAT1 using MALAT1-locked nucleic acid GapmeR significantly attenuated KLF2 and CD31 protein expression after infarction induced by HBO-induced exosomes. HBO-induced exosomes also decreased infarct size significantly. HBO-induced exosomes from cardiac myocytes up-regulate MALAT1 to suppress miR-92a expression and counteract the inhibitory effect of miR-92a on KLF2 and CD31 expression in left ventricular myocardium after myocardial infarction to enhance neovascularization.

SUBMITTER: Shyu KG

PROVIDER: S-EPMC7701534 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Hyperbaric oxygen-induced long non-coding RNA MALAT1 exosomes suppress MicroRNA-92a expression in a rat model of acute myocardial infarction.

Shyu Kou-Gi KG Wang Bao-Wei BW Fang Wei-Jen WJ Pan Chun-Ming CM Lin Chiu-Mei CM

Journal of cellular and molecular medicine 20200916 22

Hyperbaric oxygen (HBO) improves angiogenesis. The effect of HBO on metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a pro-angiogenic long non-coding RNA, in cardiac myocyte-derived exosomes and acute myocardial infarction (AMI) is unknown. We aimed to investigate whether MALAT1 is altered in cardiac myocyte-derived exosomes in response to HBO as well as the molecular regulatory mechanisms of MALAT1 in cardiac myocytes treated with HBO. Cardiac myocytes were cultured, and HBO was ...[more]

PMID: 32939962

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Project description:BackgroundOxygen (O2) is widely used in people with acute myocardial infarction (AMI). Previous systematic reviews concluded that there was insufficient evidence to know whether oxygen reduced, increased or had no effect on heart ischaemia or infarct size. Our first Cochrane review in 2010 also concluded there was insufficient evidence to know whether oxygen should be used. Since 2010, the lack of evidence to support this widely used intervention has attracted considerable attention, prompting further trials of oxygen therapy in myocardial infarction patients. It is thus important to update this Cochrane review.ObjectivesTo assess the effects of routine use of inhaled oxygen for acute myocardial infarction (AMI).Search methodsWe searched the following bibliographic databases on 6 June 2015: the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE (OVID), Embase (OVID), CINAHL (EBSCO) and Web of Science (Thomson Reuters). LILACS (Latin American and Caribbean Health Sciences Literature) was last searched in September 2016. We also contacted experts to identify eligible studies. We applied no language restrictions.Selection criteriaRandomised controlled trials in people with suspected or proven AMI (ST-segment elevation myocardial infarction (STEMI) or non-STEMI) within 24 hours after onset, in which the intervention was inhaled oxygen (at normal pressure) compared to air, regardless of co-therapies provided to participants in both arms of the trial.Data collection and analysisTwo authors independently reviewed the titles and abstracts of identified studies to see if they met the inclusion criteria and independently undertook the data extraction. We assessed the quality of studies and the risk of bias according to guidance in the Cochrane Handbook for Systematic Reviews of Interventions. The primary outcome was death. The measure of effect used was the risk ratio (RR) with a 95% confidence interval (CI). We used the GRADE approach to evaluate the quality of the evidence and the GRADE profiler (GRADEpro) to import data from Review Manager 5 and create 'Summary of findings' tables.Main resultsThe updated search yielded one new trial, for a total of five included studies involving 1173 participants, 32 of whom died. The pooled risk ratio (RR) of all-cause mortality in the intention-to-treat analysis was 0.99 (95% CI 0.50 to 1.95; 4 studies, N = 1123; I2 = 46%; quality of evidence: very low) and 1.02 (95% CI 0.52 to 1.98; 4 studies, N = 871; I2 = 49%; quality of evidence: very low) when only analysing participants with confirmed AMI. One trial measured pain directly, and two others measured it by opiate usage. The trial showed no effect, with a pooled RR of 0.97 for the use of opiates (95% CI 0.78 to 1.20; 2 studies, N = 250). The result on mortality and pain are inconclusive. There is no clear effect for oxygen on infarct size (the evidence is inconsistent and low quality).Authors' conclusionsThere is no evidence from randomised controlled trials to support the routine use of inhaled oxygen in people with AMI, and we cannot rule out a harmful effect. Given the uncertainty surrounding the effect of oxygen therapy on all-cause mortality and on other outcomes critical for clinical decision, well-conducted, high quality randomised controlled trials are urgently required to inform guidelines in order to give definitive recommendations about the routine use of oxygen in AMI.

Project description:AimsNaturally secreted nanovesicles, known as exosomes, play important roles in stem cell-mediated cardioprotection. We have previously demonstrated that atorvastatin (ATV) pretreatment improved the cardioprotective effects of mesenchymal stem cells (MSCs) in a rat model of acute myocardial infarction (AMI). The aim of this study was to investigate if exosomes derived from ATV-pretreated MSCs exhibit more potent cardioprotective function in a rat model of AMI and if so to explore the underlying mechanisms.Methods and resultsExosomes were isolated from control MSCs (MSC-Exo) and ATV-pretreated MSCs (MSCATV-Exo) and were then delivered to endothelial cells and cardiomyocytes in vitro under hypoxia and serum deprivation (H/SD) condition or in vivo in an acutely infarcted Sprague-Dawley rat heart. Regulatory genes and pathways activated by ATV pretreatment were explored using genomics approaches and functional studies. In vitro, MSCATV-Exo accelerated migration, tube-like structure formation, and increased survival of endothelial cells but not cardiomyocytes, whereas the exosomes derived from MSCATV-Exo-treated endothelial cells prevented cardiomyocytes from H/SD-induced apoptosis. In a rat AMI model, MSCATV-Exo resulted in improved recovery in cardiac function, further reduction in infarct size and reduced cardiomyocyte apoptosis compared to MSC-Exo. In addition, MSCATV-Exo promoted angiogenesis and inhibited the elevation of IL-6 and TNF-α in the peri-infarct region. Mechanistically, we identified lncRNA H19 as a mediator of the role of MSCATV-Exo in regulating expression of miR-675 and activation of proangiogenic factor VEGF and intercellular adhesion molecule-1. Consistently, the cardioprotective effects of MSCATV-Exo was abrogated when lncRNA H19 was depleted in the ATV-pretreated MSCs and was mimicked by overexpression of lncRNA H19.ConclusionExosomes obtained from ATV-pretreated MSCs have significantly enhanced therapeutic efficacy for treatment of AMI possibly through promoting endothelial cell function. LncRNA H19 mediates, at least partially, the cardioprotective roles of MSCATV-Exo in promoting angiogenesis.

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Hyperbaric oxygen-induced long non-coding RNA MALAT1 exosomes suppress MicroRNA-92a expression in a rat model of acute myocardial infarction.

Publications

Hyperbaric oxygen-induced long non-coding RNA MALAT1 exosomes suppress MicroRNA-92a expression in a rat model of acute myocardial infarction.

Similar Datasets

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