Project description:To explore the differences in the expression of circRNA in myocardial ischemia-reperfusion injury and the potential effects of these differences in circRNA. Methods 6 SPF male SD rats were randomly divided into two groups, including 3 in Myocardial ischemia reperfusion group and 3 threading without ligation in control group by ligating the left anteriors branch for 40 minutes and reperfusing for 2 hours to establish a model of myocardial ischemia reperfusion injury. The myocardial specimens from the infarct area were taken for high-throughput sequencing analysis to obtain differently expressed circRNA. After that, GO and KEGG analysis were performed to speculate on the biological functions and possible biological pathways involved. RT-qPCR was used to verify the sequencing results of differential circRNA, and bioinformatics analysis predicted that circRNA could combine with miRNA to construct a visual network diagram and their interaction. Results Analyzing of 13576 circRNAs detected in 6 rats from MIRI group and control group, A total of 132 circRNAs showed significant differential expression, of which 82 were up-regulated and 50 were down-regulated. The results of GO and KEGG analysis suggest that differential circRNA is closely related to myocardial ischemia reperfusion injury, and KEGG analysis suggests that differential circRNA is involved in calcium, AMPK, mTOR and adrenaline signal pathways. 4 circRNAs were extracted from the up-regulated circRNA for RT-qPCR verification, and the results of 2 were consistent with the high-throughput sequencing results. circRNA-miRNA interaction analysis shows that circRNA interacts with a variety of miRNAs. Conclusions The expression of circRNA in myocardial reperfusion injury rats is significantly different, which may be involved in the occurrence and development of myocardial ischemia-reperfusion injury through miRNA sponge action of circRNA.
Project description:CircRNAs have complex biological functions and are involved in the development of several cardiovascular diseases. The relationship between circRNAs and myocardial ischaemia-reperfusion injury (MIRI) is not yet clear. The aim of this study was to investigate the expression of circRNAs in rat plasma, to examine the differential expression profile of circRNAs in the plasma of MIRI rats, and to explore whether these circRNAs are potentially significant and have potential as novel markers for the diagnosis of MIRI and as therapeutic targets.
Project description:This study aimed to investigate the cardioprotective mechanism of baicalin (BAI) against myocardial ischemia-reperfusion injury (MIRI) in rats. We performed RNA-seq on left ventricular myocardial tissue from three groups: Sham (vehicle control), I/R (ischemia-reperfusion injury model), and I/R+BAI (baicalin treatment 100 mg/kg administered 10 min prior to reperfusion). The goal was to identify differentially expressed genes and key biological pathways affected by baicalin treatment. Transcriptomic analysis revealed that baicalin reversed I/R-induced activation of innate immune pathways, including complement activation, neutrophil degranulation, and TLR signaling.
Project description:Mitochondrial Creatine Kinase 2 (Ckmt2) as a Plasma-Based Biomarker for Evaluating Reperfusion Injury in Acute Myocardial Infarction
Project description:This SuperSeries is composed of the following subset Series: GSE21405: MicroRNA Profiling In Ischemia-Reperfusion Injury Of The Gracilis Muscle In Rats GSE21406: Potential Target Genes of MicroRNA-21 In Ischemia-Reperfusion Injury Of The Gracilis Muscle In Rats Refer to individual Series
Project description:Background: Ischemic preconditioning (IPC), i.e., brief periods of ischemia, protect the heart from subsequent prolonged ischemic injury, and reduces infarction size. Myocardial stunning refers to transient loss of contractility in the heart after myocardial ischemia that recovers without causing permanent damage. The relationship between IPC and myocardial stunning remains incompletely understood. Purpose: The primary aim of this study was to examine the effects of IPC on the relationship between ischemia duration, stunning, and infarct size in an ischemia-reperfusion injury model. The secondary aim of the study was to examine to which extent the phosphoproteomic changes induced by IPC relate to myocardial contractile function. Methods: Rats were subjected to different durations of left anterior descending artery (LAD) occlusion, with or without preceding IPC. Echocardiograms were acquired at 4 and 48 hours to assess cardiac contraction in the affected myocardial segment. Reversible akinesia was defined as the presence of myocardial akinesia at 4 hours that resolved by 48 hours; and was considered to represent myocardial stunning. Infarction size was evaluated using triphenyl tetrazolium chloride staining. Phosphoproteomic analysis was performed in heart tissue from preconditioned and non-preconditioned animals using nano-liquid chromatography-mass spectrometry. Results: Reversible akinesia was observed in a majority of the rats that were subjected to IPC and subsequently exposed to ischemia of 13.5 or 15 minutes of ischemia (83.3% [n/N] and 66.6% [n/N] respectively). Among rats without IPC, who were exposed to either 10, 11, 12 or 13.5 minutes of ischemia, reversible akinesia was observed in 0% (n/N), 17% (2/12), 0% (n/N) and 0% (n/N) of rats (p<0.001). Phosphoproteomic analysis revealed significant differential regulation of 809 phosphopeptides between IPC and non-IPC groups, with significant associations with the sarcomere, Z-disc, and actin binding. Conclusion: Our study shows that IPC preferentially induces changes in phosphosites of proteins involved in myocardial contraction, and both increases the incidence of reversible post-ischemic myocardial stunning after ischemia-reperfusion injury and reduces infarction size.
Project description:This study aims to investigate the dynamic changes and correlation of no-reflow (NR) injury following myocardial ischemia and reperfusion, and to explore the underlying mechanism of NR injury through transcriptomic and metabolomic analysis. Methods: Healthy male SD rats were divided into two batches: fixed ischemia time and fixed reperfusion time. In the model group, the left anterior descending coronary artery was ligated and subsequently reperfused, while the Sham group, underwent threading without ligation. The myocardial area with NR and the ischemia area were assessed using thioflavin S and Evans blue staining, the cardiac function was measured by echocardiography, the myocardial enzyme activity was detected by automatic biochemical analyzer, and the mechanisms of NR phenomenon were analyzed via transcriptomic and metabolomic approaches, with validation through Western blot (WB) analysis. Results: The model group showed obvious NR phenomenon. During fixed reperfusion, NR and ischemia were the largest at 4 h of ischemia. In fixed ischemia, NR and ischemia area were the largest when reperfusion was performed for 24 hours. Compared with the Sham group, the myocardial enzyme activity of the rats in the vast majority of the model group was increased, and the cardiac function of the rats in all model groups was impaired. Metabolomics results showed that the main differential metabolites were citric acid and succinic acid, etc when NR occurred, and the main pathways there oxidative phosphorylation and TCA cycle. Transcriptome analysis showed that the expression levels of branched-chain aminotransferase 1 (Bcat1), 4-hydroxyphenylpyruvate dioxygenase (HPD) and glutathione transferase Zeta 1 (GSTZ1) were changed when NR occurred. The results of the enrichment of transcriptome biological functions involve tyrosine metabolism, etc., and are related to amino acid metabolites related to the TCA cycle. Metabolomics and transcriptomics results were analyzed using MetaboAnalyst 6.0 to show that when NR occurs, it affects energy metabolism and causes NR damage by regulating the TCA cycle, which is mainly related to the metabolism of amino acids such as tyrosine. WB results showed that the protein expression of Bcat1, HPD and GSTZ1 decreased after NR injury.