Blood milieu in acute myocardial infarction reprograms human macrophages for trauma repair
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE215801 | GEO | 2022/12/18
REPOSITORIES: GEO
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Project description:Aberrant production and/or function of multiple host systemic factors (e.g., metabolic and immune-inflammatory mediators) act in concert to promote a âtumorigenicâ host milieu that directly promotes an aggressive malignant phenotype as well as drug resistance. Hence, strategies with the capacity to simultaneously act across multiple host systemic pathways may be required to optimize therapeutic outcomes in solid tumors. We hypothesized that chronic aerobic training, a pleiotropic whole-body intervention, modulates multiple systemic host pathways that, in turn, effectively alters cancer cell phenotype in vitro. Plasma samples from patients with solid tumors exposed to chronic aerobic training or sedentary control were comprehensively characterized for changes in immune, inflammatory, and metabolic pathways. Compared with sedentary control, aerobic training caused significant reductions in interleukin (IL)-4, macrophage inflammatory protein-1 beta (MIP1-β), vascular endothelial growth factor (VEGF), tumor necrosis factor-alpha (TNF-α), and hepatocyte growth factor (HGF). There were no significant changes in leukocyte phenotype or any plasma metabolite signatures. Exposure of estrogen receptor (ER) distinct human breast cancer cell lines (MCF-7 and MDA-MB-231) to post-intervention serum from breast cancer patients exposed to aerobic training caused marked increases in proliferation, migration, and apoptosis, compared to control patient serum. Only the combination of cytokines significantly reduced in plasma following aerobic training recapitulated the phenotype observed with patient serum in MCF-7 cells whereas only the single addition of MIP-1β or HGF significantly increased apoptosis in MDA-MB-231 cells. Co-culturing of MDA-MB-231 cells with patient exercise serum and a HGF neutralizing antibody increased proliferation and completely abrogated exercise serum-induced apoptosis. Finally, whole-genome microarray of MDA-MB-231 cells exposed to exercise or control patient serum revealed differential modulation of 310 genes including PTEN, CDK3, and IGFBP1. Our findings indicate the widespread potential of chronic aerobic training to modulate host immune-inflammatory systemic factors in patients with solid tumors. Modulation of such pathways directly alters breast cancer phenotypes providing novel insight into the molecular pathways by which exercise may inhibit malignant progression. MDA-MB-231 cells were plated at 250,000 cells/well in triplicate with 10% FBS in 6-well plates and left overnight to adhere. Media was suctioned off and replaced with serum free media. Patient serum was then added to the wells at a 10% final concentration and RNA was harvested using Qiagen RNeasy kit after 4 days.
2013-08-01 | E-GEOD-46925 | biostudies-arrayexpress
Project description:Aberrant production and/or function of multiple host systemic factors (e.g., metabolic and immune-inflammatory mediators) act in concert to promote a ‘tumorigenic’ host milieu that directly promotes an aggressive malignant phenotype as well as drug resistance. Hence, strategies with the capacity to simultaneously act across multiple host systemic pathways may be required to optimize therapeutic outcomes in solid tumors. We hypothesized that chronic aerobic training, a pleiotropic whole-body intervention, modulates multiple systemic host pathways that, in turn, effectively alters cancer cell phenotype in vitro. Plasma samples from patients with solid tumors exposed to chronic aerobic training or sedentary control were comprehensively characterized for changes in immune, inflammatory, and metabolic pathways. Compared with sedentary control, aerobic training caused significant reductions in interleukin (IL)-4, macrophage inflammatory protein-1 beta (MIP1-β), vascular endothelial growth factor (VEGF), tumor necrosis factor-alpha (TNF-α), and hepatocyte growth factor (HGF). There were no significant changes in leukocyte phenotype or any plasma metabolite signatures. Exposure of estrogen receptor (ER) distinct human breast cancer cell lines (MCF-7 and MDA-MB-231) to post-intervention serum from breast cancer patients exposed to aerobic training caused marked increases in proliferation, migration, and apoptosis, compared to control patient serum. Only the combination of cytokines significantly reduced in plasma following aerobic training recapitulated the phenotype observed with patient serum in MCF-7 cells whereas only the single addition of MIP-1β or HGF significantly increased apoptosis in MDA-MB-231 cells. Co-culturing of MDA-MB-231 cells with patient exercise serum and a HGF neutralizing antibody increased proliferation and completely abrogated exercise serum-induced apoptosis. Finally, whole-genome microarray of MDA-MB-231 cells exposed to exercise or control patient serum revealed differential modulation of 310 genes including PTEN, CDK3, and IGFBP1. Our findings indicate the widespread potential of chronic aerobic training to modulate host immune-inflammatory systemic factors in patients with solid tumors. Modulation of such pathways directly alters breast cancer phenotypes providing novel insight into the molecular pathways by which exercise may inhibit malignant progression.
2013-08-01 | GSE46925 | GEO
Project description:Abusive head trauma (AHT) is a leading cause of mortality and morbidity in infants. We explored novel AHT biomarkers via untargeted proteomics of peripheral postmortem blood (PMB) specimens collected during medico-legal autopsies of infants. The panel of PMB biomarkers was confirmed in antemortem serum samples as a potential signature capable of being applied to living patients to support AHT screening and improve their prognosis through early medical care.
2023-01-07 | PXD028801 | Pride
Project description:The study was aimed to identify mechanisms linked to complicated courses after severe trauma by a systems biology approach. In severe trauma, overwhelming systemic inflammation can result in adverse events and the development of complications, including sepsis. In a prospective study, RNA samples from circulating leukocytes from patients with multiple injury (injury severity score ⥠17) were analyzed for dynamic changes in gene expression over a period of 21 days by whole genome screening. Based on their clinical presentation, patients were divided into two subgroups: patients with secondary sepsis after trauma (n=5) and patients with systemic inflammation without infection (n=5). Expression cluster were defined by correlating gene expression data with clinical outcome parameters. Using unsupervised clustering, patients with systemic inflammation only and patients with sepsis showed a distinct expression pattern and the discrimination of clinical presentation was reflected by clustering of the samples. Explorative gene set analysis revealed robust upregulation of genes related to âhemoglobin metabolism/oxygen transportâ and âpathogenic E.coli infectionâ. 10 patients with multi-system trauma (ISS ⥠17 points) admitted to the Division of Trauma Surgery at the University Hospital Zurich were included. Whole blood from trauma patients was collected within the first 6 h after trauma (day 0) and on days 1, 2, 3, 5, 7, 10, 14, and 21. Total cellular RNA from circulating leukocytes was isolated using PaxGene Blood RNA Kit (PreAnalytix) for transcriptome profiling. RNA from blood of trauma patients was extracted and subjected to microarray analysis for comparison of longitudinal transcriptomic responses of patients. RNA samples of circulating leukocytes covering time points directly after admission (D0) and on the consecutive days (D1-D21) were subject to multifactorial microarray data analysis: Differences in dynamics of transcripts were assessed by contrasting time- and individual-resolved changes for sepsis and systemic inflammation without infection.
2015-11-01 | E-GEOD-70311 | biostudies-arrayexpress
Project description:The study was aimed to identify mechanisms linked to complicated courses after severe trauma by a systems biology approach. In severe trauma, overwhelming systemic inflammation can result in adverse events and the development of complications, including sepsis. In a prospective study, RNA samples from circulating leukocytes from patients with multiple injury (injury severity score ≥ 17) were analyzed for dynamic changes in gene expression over a period of 21 days by whole genome screening. Based on their clinical presentation, patients were divided into two subgroups: patients with secondary sepsis after trauma (n=5) and patients with systemic inflammation without infection (n=5). Expression cluster were defined by correlating gene expression data with clinical outcome parameters. Using unsupervised clustering, patients with systemic inflammation only and patients with sepsis showed a distinct expression pattern and the discrimination of clinical presentation was reflected by clustering of the samples. Explorative gene set analysis revealed robust upregulation of genes related to ‘hemoglobin metabolism/oxygen transport’ and ‘pathogenic E.coli infection’.
2015-11-01 | GSE70311 | GEO
Project description:Background: Aortic valve sclerosis (AVSc) presents similar pathogenetic mechanisms to coronary artery disease (CAD) and is associated with both short- and long-term mortality. In the context of acute myocardial infarction (AMI), evidence of specific systemic mechanisms characterizing AVSc are currently lacking. Objective: To evaluate the systemic pathophysiological landscape that might differentiate AVSc from non-AVSc subjects in AMI. Methods: Whole-blood transcriptome of AVSc (n=44) and no-AVSc (n=66) patients with AMI was assessed by RNA-sequencing. A bioinformatic workflow, including feature selection, differential expression and enrichment analysis was performed to identify gene expression signatures discriminating AVSc from no-AVSc and infer functional association. Multivariable Cox regression analysis was used to estimate hazard ratio of AVSc versus no-AVSc patients. Results: A signature of 100 informative genes allowed classifying AVSc from no-AVSc with 94% accuracy. Significant differences in 143 genes were also identified, 30 of which withstood association independently of age and previous AMI, or cardiac interventions. Functional inference unveiled significant association of AVSc with acute inflammatory and type I interferons (IFNs) response, platelet activation and hemostasis. AMI patients with AVSc showed a significantly higher incidence of adverse cardiovascular events within 10 years of follow-up with a full adjusted hazard ratio of 2.4 (95% CI 1.3–4.5). Conclusions: During AMI, AVSc patients showed increased type I IFNs response and associated adverse cardiovascular outcomes at follow-up. Novel pharmacological therapies aiming to inhibit response to type I IFNs during or immediately after AMI might improve poor cardiovascular outcomes of AMI patients with AVSc.
2024-01-31 | GSE218474 | GEO
Project description:Itaconate-producing neutrophils regulate local and systemic inflammation following trauma
2023-11-08 | GSE221134 | GEO
Project description:In this study human primary monocyte-derived macrophages from healthy volunteers (pool of 6-8 donors) were exposed for 24 h to a 1:5 dilution of human patient serum. Patient sera were obtained either from control patients (n=20) or patients suffering an acute myocardial infarction (AMI, n=47, selected from POSTEMI trial, S. Limalanathan et al. J Am Heart Assoc 2014). All exposed macrophages were analyzed by RNA sequencing. The study revealed that macrophages significantly alter their gene expression profile in response the AMI-serum exposure, and adapt phagocytic, metabolic and cell cycling programs.
2022-12-18 | GSE172270 | GEO
Project description:Background: Stress cardiomyopathy (SCM) is a unique form of LV dysfunction that more often occurs in women. Patients with SCM have a higher Troponin I/B-type natriuretic peptide ratio than AMI, but little is known about other circulating proteins. The goals of this study were to compare plasma proteins in SCM and AMI to learn about the pathophysiology of SCM and also to identify putative biomarkers of SCM. Methods: Blood was drawn in normal controls (n=6), women with AMI (n=12) or women with acute SCM (n=15). Two-week follow up samples were available in AMI (n=4) and SCM patients (n=11). Relative concentrations of 1310 serum proteins were measured in each of the 48 samples using the SOMAscan aptamer based assay. Women with AMI tended to be younger (57.87 ± 16.0 vs. 65.08 ± 9.11 years, p=0.12) and had a higher peak troponin I (AMI 32.03 ± 29.46 vs. SCM 2.68 ± 2.6 ng/mL, p=0.02). No differentially expressed proteins were detected (absolute log2 fold change>1; q<0.05) between AMI and SCM in the acute or recovery phase. In the normal vs. AMI comparison there was differential expression of 35 proteins. In the normal vs. SCM comparison there were 45 proteins with differential expression. Pathway analysis demonstrated activation of complement, coagulation, and inflammation in both AMI and SCM. Conclusions: The acute phase of SCM is characterized by a severe inflammatory response similar to AMI. Despite recovery of LV function in SCM at two weeks, differences in circulating proteins remain in comparison to normal controls.
2017-08-03 | GSE95368 | GEO
Project description:Primary human macrophages were cultured 1, 3 or 6 days with different stimuli. Macrophages are key cell types of the innate immune system regulating host defense, inflammation, tissue homeostasis and cancer. Within this functional spectrum diverse and often opposing phenotypes are displayed which are dictated by environmental clues and depend on highly plastic transcriptional programs. Among these the ‘classical’ (M1) and ‘alternative’ (M2) macrophage polarization phenotypes are the best characterized. Understanding macrophage polarization in humans may reveal novel therapeutic intervention possibilities for chronic inflammation, wound healing and cancer. Systematic loss of function screening in human primary macrophages is limited due to lack of robust gene delivery methods and limited sample availability. To overcome these hurdles we developed cell-autonomous assays using the THP-1 cell line allowing genetic screens for human macrophage phenotypes. To confirm the relevance of the THP1-based system we performed microarray studies on THP1 cells and primary human cells subjected to various conditions.
2017-08-25 | E-MTAB-5913 | biostudies-arrayexpress