Propofol protects cardiomyocytes from hypoxia/reoxygenation injury via regulating MALAT1/miR‐206/ATG3 axis

Abstract

Previous studies have shown that propofol (PPF) plays a protective role in ischemia-reperfusion (I/R) in multiple organs and tissues. This study was aimed to explore the mechanism of PPF in ameliorating myocardial ischemia-reperfusion injury (MIRI). MIRI model was established with Sprague-Dawley rats, and PPF pretreatment was performed before reperfusion. Creatine kinase isoform (CK-MB), lactate dehydrogenase (LDH), and hematoxylin and eosin stain were used to evaluate the severity of MIRI. H9c2 cells were treated with hypoxia/reoxygenation (H/R) to simulate I/R injury in vitro. Real-time quantitative polymerase chain reaction (qPCR) was employed to assess MALAT1 and microRNA (miR)−206 expressions. Autophagy-related 3 (ATG3), LC3BⅡ/LC3BⅠ, and Beclin-1 expression were examined by western blot.Apoptosis was monitored using flow cytometry. Interaction between MALAT1 and miR-206 was determined by bioinformatics analysis, dual-luciferase reporter gene assay, RIP assay, and RNA pull-down assay. PPF pretreatment remarkably reduced CK-MB level, LDH level, myocardial infarct size, and LC3BⅡ/LC3BⅠ ratio and Beclin-1 expression in the rats with MIRI, and repressed the apoptosis of H9c2 cells exposed to H/R. PPF pretreatment markedly suppressed MALAT1 expression and enhanced miR-206 expression in both in vivo and in vitro models. MiR-206 was identified as a target of MALAT1 in cardiomyocytes, and MALAT1 could increase the expression of ATG3.Additionally, the upregulation of MALAT1 partially reversed the protective effect of PPF on cardiomyocytes in vitro. PPF modulated MALAT1/miR-206/ATG3 axis to protect cardiomyocytes against I/R injury.

Exosomal MALAT1 promotes the proliferation of esophageal squamous cell carcinoma through glyoxalase 1-dependent methylglyoxal removal

“…miR-206 is widely recognized as a tumor suppressor [ [38] , [39] , [40] , [41] ], and analysis based on a public database also supports its suppressor role in ESCC. The interplay between MALAT1 and miR-206 has been reported in previous studies [ 42 , 43 ], further supporting the ceRNA mechanism for the MALAT1-miR-206-KAT2B axis.…”

MiR-206 may regulate mitochondrial ROS contribute to the progression of Myocardial infarction via TREM1

“…Several studies have found that miR-206 is always expressed in the cardiovascular system and may be associated with CVD. The expression of miR-206 was markedly downregulated in the heart tissue of rats with myocardial ischemia–reperfusion injury, and the overexpression of lncRNA MALAT1 significantly suppressed miR-206 expression [ 56 ]. Another study found miR-206 mediates ox-LDL induced ECs injury [ 57 ].…”

A novel circulating biomarker lnc‐MALAT1 for acute myocardial infarction: Its relationship with disease risk, features, cytokines, and major adverse cardiovascular events

“…According to previous studies, lipid profile, cTnI, infarct size, inflammation, and adhesion molecules are viewed as hallmarks of AMI 22 , 23 , 24 ; thus, we explored the association of lnc‐MALAT1 with them among AMI patients, which showed that lnc‐MALAT1 was positively linked with lipid dysregulation (reflected by LDL‐C), the marker of myocardial injury (reflected by cTnI), disease severity indicator (reflected by infarct size), systematic inflammation (reflected by CRP, TNF‐α, IL‐6, and IL‐17A), and adhesion cytokines (reflected by VCAM‐1 and ICAM‐1). The potential explanations might be that (1) lnc‐MALAT1 could accelerate lipid metabolism and lipid oxidation in AMI, which resulted in elevated LDL‐C 25 ; (2) lnc‐MALAT1 might promote cardiomyocyte injury through several mechanisms, such as regulating autophagy‐related 3, as well as phosphatase and tensin homolog deleted on chromosome 10, which led to increased cTnI and infarct size in AMI 26 , 27 ; (3) lnc‐MALAT1 might be able to accelerate inflammation by regulating several signaling pathways, including Wnt/β‐catenin and nuclear factor‐kappa B signaling; thereby, lnc‐MALAT1 was positively associated with inflammation in AMI patients 28 , 29 ; and (4) lnc‐MALAT1 could accelerate the production of adhesion molecules through several methods, such as microRNA‐590 and the signal transducer and activator of transcription 3 pathway 21 ; thus, a positive relation was found in lnc‐MALAT1 with adhesion cytokines among AMI patients. In addition, we also discovered that higher lnc‐MALAT1 was linked with a history of DM among AMI patients.…”

“…lnc-MALAT1 could accelerate lipid metabolism and lipid oxidation in AMI, which resulted in elevated LDL-C 25 ; (2) lnc-MALAT1 might promote cardiomyocyte injury through several mechanisms, such as regulating autophagy-related 3, as well as phosphatase and tensin homolog deleted on chromosome 10, which led to increased cTnI and infarct size in AMI26,27 ; (3) lnc-MALAT1 might be able to accelerate inflammation by regulating several signaling pathways, including Wnt/β-catenin and nuclear factor-kappa B signaling; thereby, lnc-MALAT1 was positively associated with inflammation in AMI patients28,29 ; and (4) lnc-MALAT1 could accelerate the production of adhesion molecules through several methods, such as microR-NA-590 and the signal transducer and activator of transcription 3 pathway21 ; thus, a positive relation was found in lnc-MALAT1 with adhesion cytokines among AMI patients.…”