LncRNAs and mRNAs changes in border zone of myocardial infarction in rats
ABSTRACT: Comparison of both LncRNAs and mRNAs expression in the border zone of the myocardial infarction rats and the sham operation rats Border zone (BZ) of the myocardial infarction is critical to patients. Current treatments of myocardial infarction are primarily aimed to save the dying myocardial cell in the border zone. During myocardial infarction, certain changes in BZ, e.g, apoptosis, fibrosis, inflammation, etc, played an important role in deciding the survival. Impairment and recovery of BZ has been linked to gene expression changes. The aim of our study was to obtain a global expression profile of lncRNAs and mRNAs of the border zone in Wistar rats myocardial infarction, and identify the changes during myocardial infarction. Overall design: 3 male rats were used to set up myocardial infarction model by ligation of LAD, and 3 rats were sham-operated. Border zone tissue of myocardial infarction was determined by TTC&EB double stain, then was send to further microarry analysis.
INSTRUMENT(S): Arraystar Rat LncRNA microarray (026403)
Project description:To unveil the role of Angiopoietin-2 in regulating vascular remodeling after myocardial infarction Overall design: Infarct border zone endothelial cells were sorted from myocardial infarction model mice deleting Angiopoietin-2 or Wild-type control.
Project description:Very little information is available about non-coding(nc)RNAs and their role in regulating tissue responses in myocardial ischemia and acute infarction. We measured for the first time nascent RNA transcription of protein coding genes, primary(pri)-miRNAs, long non-coding(lnc)RNAs and enhancer(e)RNAs in healthy myocardium, border zone to ischemia and infarction area in pig hearts using GRO-seq. The gene expression analysis indicated a gradient of induction of inflammatory mediators, and repression of PPAR-signaling and oxidative phosphorylation. An exception to rule was A1 adenosine receptor, which exhibited induced gene expression in the border zone, where it might increase myocardial resistance to ischemia, but repression in the ischemic zone. In addition, we interrogated for the first time the transcriptional regulation of pri-miRs and provide evidence that several arrhythmia-related target genes are further repressed at post-transcriptional level. We identified 450 lncRNAs which were differently regulated by ischemia including novel lncRNAs expressed in antisense orientation to major myocardial transcription factors GATA4, GATA6 and KLF6. Finally, characterization of enhancers exhibiting differential expression of eRNAs, pointed a central role for KLF, MEF2C, ETS, NFY, ATF, E2F2 and NRF1 transcription factors in determining tissue-specific responses to ischemic insult. In conclusion, GRO-Seq allowed us to follow the gradient of gene expression occurring in the ischemic heart and identify novel ncRNAs regulated by oxygen deprivation. These findings have identified potential new targets for diagnosis and treatment of myocardial ischemia based on acute changes in eRNA, lncRNA and miRNA expression in the affected heart. Overall design: GRO-Seq from pig myocardium
Project description:MicroRNAs are important cellular components and their dysfunctions are associated with various disease. Acute myocardial infarction (AMI) is one of the most serious cardiovascular diseases. Although several miRNAs have been reported to be associated with AMI, more novel miRNAs are needed to be investigated to ascertain if they are associated with AMI. Overall design: SD rats (180-200g) was divided into sham-control group and two days group after AMI, seven days group after AMI, fourteen days group after AMI, each group has six individual animals total RNA was taken from the border-zone myocardium , low molecular weight RNA was seperate and labeled , and then hybridized to capitalbio V2 biochip representing about 924 microRNA . three chip were test in each group, and the procedure was repeated twice.
Project description:MicroRNAs are important cellular components and their dysfunctions are associated with various disease. Acute myocardial infarction (AMI) is one of the most serious cardiovascular diseases. Although several miRNAs have been reported to be associated with AMI, more novel miRNAs are needed to be investigated to ascertain if they are associated with AMI. SD rats (180-200g) was divided into sham-control group and two days group after AMI, seven days group after AMI, fourteen days group after AMI, each group has six individual animals total RNA was taken from the border-zone myocardium , low molecular weight RNA was seperate and labeled , and then hybridized to capitalbio V2 biochip representing about 924 microRNA . three chip were test in each group, and the procedure was repeated twice.
Project description:Myocardial infarction (MI) is a highly prevalent cardiac emergency, which results in adverse left ventricular remodeling exacerbating progressive heart failure. Inflammation in post-MI is necessary for myocyte repair and wound healing. However, it is also a key component of subsequent heart failure pathology. Myoblasts transplantation after MI have been fulfilled a good effect on cardiac repair, but the occasion, complications of transplantation, and the underlying mechanisms have not been fully elucidated. Here, we found that myoblast transplantation decreased the expression of many pro-inflammatory genes and the activation of inflammation-related signal pathway in heart tissue of pig post MI, which mainly contributed to the improved heart function and attenuated damage of myocardial cells. Overall design: We constructed a minipig surgical model of myocardial infarction. Myoblasts were intramyocardially injected into the infarct and border zone of heart. The infarct and border zone heart tissues from minipigs treated with myoblast transplantation or untreated control (one sample for every group) were submitted for gene expression array analysis.
Project description:Affymetrix microarray analysis of molecular changes after myocardial infarction. Samples of heart tissue were analyzed after myocardial infarction from WT and reg3beta knock-out mice. Samples from scar tissue and samples adjacent to the scar were analyzed. In the experiment we primarily compared infarction zone of wild-type to infarction zone of knock-out animals, and remote zone of wild-type to remote zone of knock-outs.
Project description:In contrast to mammals, zebrafish regenerate heart injuries via proliferation of cardiomyocytes located at the wound border. Here, we show that tomo-seq can be used to identify whole-genome transcriptional profiles of the injury zone, the border zone and the healthy myocardium. Interestingly, the border zone is characterized by the re-expression of embryonic cardiac genes that are also activated after myocardial infarction in mouse and human, including targets of Bone Morphogenetic Protein (BMP) signaling. Endogenous BMP signaling has been reported to be detrimental to mammalian cardiac repair. In contrast, we find that genetic or chemical inhibition of BMP signaling in zebrafish reduces cardiomyocyte dedifferentiation and proliferation, ultimately compromising myocardial regeneration, while bmp2b overexpression is sufficient to enhance it. Our results provide a resource for further studies on the molecular regulation of cardiac regeneration and reveal intriguing differential cellular responses of cardiomyocytes to a conserved signaling pathway in regenerative versus non-regenerative hearts. To generate spatially-resolved RNA-seq data for injured zebrafish hearts (3 and 7 days-post-injury), we cryosectioned samples, extracted RNA from the individual sections, and amplified and barcoded mRNA using the CEL-seq protocol (Hashimshony et al., Cell Reports, 2012) with a few modifications. Libraries were sequenced on Illumina NextSeq using 75bp paired end sequencing.
Project description:Thyroid hormone improves left ventricular remodeling and cardiac performance after myocardial infarction (MI), but the molecular basis is unknown. This study was designed to detect gene expression changes in left ventricular non-infarcted areas at 4 weeks following myocardial infarction with and without thyroid hormone treatment. The results suggest that altered expression of genes for molecular function and biological process may be involved in the beneficial effects of thyroid hormone treatment following myocardial infarction in rats. MI was produced by ligation of the left anterior descending coronary artery in female SD rats. Rats were divided into the following groups: (1) Sham MI, (2) MI, and (3) MI+T4 treatment (T4 pellet 3.3mg, 60 days release, implanted subcutaneously immediately following MI). Four weeks after surgery, total RNA was isolated from left ventricular non-infarcted areas for microarray analysis using the Illumina RatRef-12 Expression BeadChip Platform.
Project description:Myocardial infarction (MI) often results in left ventricular (LV) remodeling followed by heart failure (HF). It is of great clinical importance to understand the molecular mechanisms that trigger transition from compensated LV injury to HF and to identify relevant diagnostic biomarkers. In this study, we performed transcriptional profiling of LVs in rats with a wide range of experimentally induced infarct sizes and of peripheral blood mononuclear cells (PBMCs) in animals that developed HF. We used microarrays to investigate gene expression in the left ventricle (LV) accompanying myocardial infarction and concomitant heart failure (HF) in a well validated model of post-infarcted heart failure and to evaluate their reflection in peripheral blood mononuclear cells (PBMCs) Myocardial infarction (MI) was induced in male Wistar rats by ligation of the proximal left coronary artery. The sham-operated group (control group) was subjected to the same protocol, except that the suture was not tied around the proximal left coronary artery. Sham-operated rats (n=6) and rats with small (n=6), moderate (n=6), and large (n=5) MI size were included into the experiment two months after the operation. Then, left ventricules and blood samples were obtained for RNA extraction and hybridization on Affymetrix microarrays. Microarrays were used to compare the LV and PBMCs transcriptomes of control and experimental animals. The development of heart failure was estimated by echocardiography and catheterization.