Transcriptomic profiles reveal differences between remote and ischemic myocardium after acute myocardial infarction in swine model
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PROVIDER: PRJNA882030 | ENA |
REPOSITORIES: ENA
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Project description:The purpose of this study was to unravel the differences in the molecular profile between ischemic and remote myocardium after AMI.
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Project description:Restoration of blood flow is the definitive therapy to salvage myocardium following ischemic injury. However, sudden restoration of blood flow to the ischemic myocardium causes ischemia reperfusion injury (IRI). Here, the cardioprotective effect of remote ischemic postconditioning (RPostC) was investigated, based on our in vitro rat model of myocardial IRI. Three groups, including Sham, IRI, and IRI+ RPostC, were utilized for the analysis of Affymetrix Rat Gene 2.0 ST chip.
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Project description:Introduction: Cardiac ischemic reperfusion injury (IRI) is paradoxically instigated by re-establishing blood-flow to ischemic myocardium typically from a myocardial infarction (MI). Although revascularization following MI remains the standard of care, effective strategies remain limited to prevent or attenuate IRI. We hypothesized that epicardial placement of human placental amnion/chorion (HPAC) grafts will protect against IRI. Methods: Using a clinically relevant model of IRI, swine were subjected to 45 minutes percutaneous ischemia followed with (MI+HPAC, n=3) or without (MI only, n=3) HPAC. Cardiac function was assessed by echocardiography, and regional punch biopsies were collected 14 days post-operatively. A deep phenotyping approach was implemented by using histological interrogation and incorporating global proteomics and transcriptomics in non-ischemic, ischemic, and border zone biopsies. Results: Our results established HPAC limited the extent of cardiac injury by 50% (11.02.0% vs 22.03.0%, p=0.039) and preserved ejection fraction in HPAC-treated swine (46.8±2.7% vs 35.8±4.5%, p=0.014). We present comprehensive transcriptome and proteome profiles of infarct (IZ), border (BZ), and remote (RZ) zone punch biopsies from swine myocardium during the proliferative cardiac repair phase 14 days post-MI. Both HPAC-treated and untreated tissues showed regional dynamic responses, whereas only HPAC-treated IZ revealed active immune and extracellular matrix remodeling. Decreased endoplasmic reticulum (ER)-dependent protein secretion and increased anti-apoptotic and anti-inflammatory responses were measured in HPAC-treated biopsies. Discussion: We provide quantitative evidence HPAC reduced cardiac injury from MI in a preclinical swine model, establishing a potential new therapeutic strategy for IRI.
2023-05-30 | GSE228096 | GEO
Project description:Interventions: total intravenous anesthesia:Propofol anesthesia;Sevoflurane posttreatment:Sevoflurane anesthesia;Propofol combined with sevoflurane anesthesia:Propofol combined with sevoflurane anesthesia;RIPC and propofol anesthesia:Remote ischemic preconditioning and propofol anesthesia;RIPC and sevoflurane posttreatment:Remote ischemic preconditioning and sevoflurane anesthesia;RIPC and propofol combined with sevoflurane anesthesia:Remote ischemic preconditioning and propofol combined with sevoflurane anesthesia
Primary outcome(s): blood pressure;heart rate;SPO2%;Blood gas analysis;Central venous pressure;H-FABP;cTnI;TNF-a;IL-8
Study Design: Parallel
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Project description:The use of cDNA microarrays has made it possible to analyze expression of thousands of genes simultaneously. We employed microarray gene expression profiling of porcine cDNA to compare myocardial gene expression in infarct core and remote myocardium at 1 week (n=3), 4 weeks (n=3), and 6 weeks (n=3) after surgically induced myocardial infarction (MI) and in sham-operated controls (n=3). More than 8,000 cDNA sequences were identified in myocardium that showed differential expression in response to MI. Different temporal and spatial patterns of gene expression were recognized in the infarct core tissue within this large set of data. Microarray gene profiling revealed candidate genes, some of them described for the first time, which elucidate changes in biological processes at different stages after MI. We evaluated temporal gene expression in a porcine model of myocardial infarction by microarray technology. Nine female pigs (Sus scrofa crossbreed Landrace x Large White) weighing 30-40 kg were subjected to experimental MI by a double-ligation of the first marginal branch of the circumflex artery. Animals were randomly sacrificed at 1 week (n=3), 4 weeks (n=3), or 6 weeks (n=3) after MI. Three paired myocardial samples from the infarct core and remote myocardium were analyzed at each time point. Myocardial samples from sham-operated animals (open-chest cardiac exposure without coronary artery ligation; n=3) were included as physiological controls.
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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.
2015-06-29 | E-MTAB-2561 | biostudies-arrayexpress
Project description:The molecular mechanism underlying cardiac remodeling following myocardial infarction have been incompletely understood. Until now, most studies have been performed in rodents. We studied cardiac remodeling in the physiologically more relevant animal model, the swine. Microarray analysis was performed on animals that underwent either sham surgery or permanent ligation of the left coronary artery (MI). RNA was isolated from the remote, non-ischemic, regions of the left ventricle.
2011-12-21 | GSE27962 | GEO
Project description:Cardiac sarco(endo)plasmic reticulum calcium ATPase-2 (SERCA2) plays one of the central roles in myocardial contractility. Both, SERCA2 mRNA and protein are reduced in myocardial infarction (MI), but the correlation has not been always observed. MicroRNAs (miRNAs) act by targeting 3'-UTR mRNA, causing translational repression in physiological and pathological conditions, including cardiovascular diseases. The aim of our study was to identify miRNAs that could influence SERCA2 expression in human MI. The protein SERCA2 was decreased and 43 miRNAs were deregulated in infarcted myocardium compared to remote myocardium. miRNAs binding prediction to SERCA2 identified 213 putative miRNAs. TAM and miRNApath identified 18 functional and 21 diseased states related to heart diseases. Combing all results, we identified certain miRNAs as potential regulators of SERCA2. All the samples were stored as FFPE tissue and in RNAlater. Expression of SERCA2 was analyzed by western blot and miRNA expression was analyzed by microarrays and qPCR in samples of remote and infarcted myocardium from 6 patients who died of MI. Bioinformatic analysis including six prediction programmes (TargetScan, PicTar, miRBase, miRDB, Human MicroRNA Targets, and microrna.org), TAM and miRNApath annotation, and free-energy of binding (RNA22, RNAfold), was performed. Nine up-regulated miRNAs were analyzed for free-energy of binding and flanking regions, and nine miRNAs were used for validation with qPCR. Based on qPCR the comparison between FFPE and RNAlater as well as different reference genes was also performed.
2012-04-29 | E-GEOD-17304 | biostudies-arrayexpress
Project description:The molecular mechanism underlying cardiac remodeling following myocardial infarction have been incompletely understood. Until now, most studies have been performed in rodents. We studied cardiac remodeling in the physiologically more relevant animal model, the swine. Microarray analysis was performed on animals that underwent either sham surgery or permanent ligation of the left coronary artery (MI). RNA was isolated from the remote, non-ischemic, regions of the left ventricle. RNA was isolated from 8 sham and 8 MI animals three weeks after surgery. Each group contained 4 males and 4 females. Animals used for the study were 2-3 months old Yorkshire x Landrace swine. Only neutered males entered the study.
2011-12-21 | E-GEOD-27962 | biostudies-arrayexpress
Project description:H3K9me2 ChIP-Seq of cardiac biopsies from the area at at risk and remote myocardium of mice subjected to ischemic preconditioning. Mice were subjected to ischemic preconditioning (IPC) through reversible ligation of the left coronary artery or a sham procedure. The procedure consisted of 5 minutes of ischemia followed by 5 minutes of reperfusion, repeated 4 times and then followed by a 30 minute reperfusion period. Biopsies were taken from the area at risk (AAR) and remote myocardium (RM) from six IPC mice
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