Single-cell multiomic analysis identifies macrophage subpopulations in promoting cardiac repair
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE235275 | GEO | 2024/09/06
REPOSITORIES: GEO
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Project description:Myocardial infarction (MI) is the leading cause for hear failure (HF). Following MI, the non-infarcted region of left ventricle (LV) is critical for maintaining heart function, and disruption of the LV contributes greatly to post-MI HF. Transcriptomic profiling by high-throughput sequencing was performed in a chronic HF pig model, to explore the molecular changes in the post-MI LV related to cardiovascular deterioration. Samples were taken from heart tissue of MI-induced pigs and from control pigs not subjected to MI. Regions of the heart where samples were taken included the site of ischemia (LV ischemia), area bordering ischemia (LV border), area remote to ischemia (LV remote) and the right ventricle (RV).
2021-10-04 | E-MTAB-8856 | biostudies-arrayexpress
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.
2013-03-01 | E-GEOD-34569 | biostudies-arrayexpress
Project description:Tissue repair after myocardial infarction (MI) is guided by incompletely defined autocrine and paracrine-acting proteins. Deciphering these signals and their upstream triggers is essential when considering infarct healing as a therapeutic target. Searching for previously unknown growth factors involved in infarct repair, we performed a bioinformatic secretome analysis in cardiac endothelial cells and identified cysteine-rich with EGF-like domains 2 (CRELD2), an endoplasmic reticulum stress-inducible protein with poorly characterized function. CRELD2 was abundantly expressed and secreted in the heart after MI in mice and patients. Creld2-deficient mice and wild-type mice treated with a CRELD2-neutralizing antibody displayed impaired de novo microvessel formation in the infarct border zone and developed severe postinfarction heart failure. CRELD2 protein therapy, conversely, improved heart function after MI. Exposing human coronary artery endothelial cells to recombinant CRELD2 induced angiogenesis, associated with a distinct phosphoproteome signature. These findings identify CRELD2 as a novel angiogenic growth factor and unravel a link between endoplasmic reticulum stress and ischemic tissue repair.
2023-11-30 | PXD045013 | Pride
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.
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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.
2013-03-01 | GSE34569 | GEO
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2010-05-27 | E-GEOD-19322 | biostudies-arrayexpress
Project description:Closed-chest reperfused MI was induced in pigs by 90-min occlusion, followed by reperfusion of the mid LAD (day 0) and by cardiac MRI with late enhancement (LE) at day 3. At day 30 the animals received either porcine APOSEC (n=8) or placebo medium (n=8) in a randomized manner, injected into the border zone of MI using 3D NOGA percutaneous intramyocardial guidance. At day 60, control cardiac MRI with LE and measurements of myocardial viability via diagnostic NOGA were performed. Gene expression profiling of the infarct core, border zone and normal myocardium was performed using microarray analysis, confirmed by quantitative real-time PCR. Percutaneous endomyocardial injections of APOSEC led to a significant (p<0.05) decrease in infarct size and in improvement of cardiac index and myocardial viability compared to medium treatment. Trend towards higher LV ejection fraction was observed in APOSEC vs. the Medium placebo group (45.4M-BM-15.9% vs 37.4M-BM-18.9%, p=0.052). Transcriptome analysis revealed significant downregulation of caspase-1 and other inflammatory genes in the APOSEC-affected areas. PCR showed higher expression of myogenic factor, Mefc2 (p<0.05) gene with downregulated caspase-3 (p<0.05) in the APOSEC-pigs. We have investigated the effects of catheter-based endomyocardial injections of APOSEC (secretome of apoptotic peripheral white blood cells) on porcine chronic post-infarction (MI) left ventricular (LV) dysfunction and gene expression profile. Pigs randomized to receive eithersecretome (n=8) or medium (placebo control, n=8)
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