Dataset Information

Altered gene expression pattern in peripheral blood mononuclear cells in patients with acute myocardial infarction.

ABSTRACT:

Background

Despite a substantial progress in diagnosis and therapy, acute myocardial infarction (MI) is a major cause of mortality in the general population. A novel insight into the pathophysiology of myocardial infarction obtained by studying gene expression should help to discover novel biomarkers of MI and to suggest novel strategies of therapy. The aim of our study was to establish gene expression patterns in leukocytes from acute myocardial infarction patients.

Methods and results

Twenty-eight patients with ST-segment elevation myocardial infarction (STEMI) were included. The blood was collected on the 1(st) day of myocardial infarction, after 4-6 days, and after 6 months. Control group comprised 14 patients with stable coronary artery disease, without history of myocardial infarction. Gene expression analysis was performed with Affymetrix Human Gene 1.0 ST microarrays and GCS3000 TG system. Lists of genes showing altered expression levels (fold change >1.5, p<0.05) were submitted to Ingenuity Pathway Analysis. Gene lists from each group were examined for canonical pathways and molecular and cellular functions. Comparing acute phase of MI with the same patients after 6 months (stable phase) and with control group we found 24 genes with changed expression. In canonical analysis three pathways were highlighted: signaling of PPAR (peroxisome proliferator-activated receptor), IL-10 and IL-6 (interleukin 10 and 6).

Conclusions

In the acute phase of STEMI, dozens of genes from several pathways linked with lipid/glucose metabolism, platelet function and atherosclerotic plaque stability show altered expression. Up-regulation of SOCS3 and FAM20 genes in the first days of myocardial infarction is observed in the vast majority of patients.

SUBMITTER: Kiliszek M

PROVIDER: S-EPMC3503717 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Publications

Altered gene expression pattern in peripheral blood mononuclear cells in patients with acute myocardial infarction.

Kiliszek Marek M Burzynska Beata B Michalak Marcin M Gora Monika M Winkler Aleksandra A Maciejak Agata A Leszczynska Agata A Gajda Ewa E Kochanowski Janusz J Opolski Grzegorz G

PloS one 20121121 11

<h4>Background</h4>Despite a substantial progress in diagnosis and therapy, acute myocardial infarction (MI) is a major cause of mortality in the general population. A novel insight into the pathophysiology of myocardial infarction obtained by studying gene expression should help to discover novel biomarkers of MI and to suggest novel strategies of therapy. The aim of our study was to establish gene expression patterns in leukocytes from acute myocardial infarction patients.<h4>Methods and resul ...[more]

PMID: 23185530

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Project description:BackgroundAcute myocardial infarction (AMI) can occur in patients with atherosclerotic disease, with or without plaque rupture. Previous studies have indicated a set of immune responses to plaque rupture. However, the specific circulating immune cell subsets that mediate inflammatory plaque rupture remain elusive.MethodsTen AMI patients were enrolled in our study (five with and five without plaque rupture; plaque characteristics were identified by optical coherence tomography). By single-cell RNA sequencing, we analyzed the transcriptomic profile of peripheral blood mononuclear cells.ResultsWe identified 27 cell clusters among 82,550 cells, including monocytes, T cells, NK cells, B cells, megakaryocytes, and CD34+ cells. Classical and non-classical monocytes constitute the major inflammatory cell types, and pro-inflammatory genes such as CCL5, TLR7, and CX3CR1 were significantly upregulated in patients with plaque rupture, while the neutrophil activation and degranulation genes FPR2, MMP9, and CLEC4D were significantly expressed in the intermediate monocytes derived from patients without plaque rupture. We also found that CD4+ effector T cells may contribute to plaque rupture by producing a range of cytokines and inflammatory-related chemokines, while CD8+ effector T cells express more effector molecules in patients without plaque rupture, such as GZMB, GNLY, and PRF1, which may contribute to the progress of plaque erosion. Additionally, NK and B cells played a significant role in activating inflammatory cells and promoting chemokine production in the plaque rupture. Cell-cell communication elaborated characteristics in signaling pathways dominated by inflammatory activation of classical monocytes in patients with plaque rupture.ConclusionsOur studies demonstrate that the circulating immune cells of patients with plaque rupture exhibit highly pro-inflammatory characteristics, while plaque erosion is mainly associated with intermediate monocyte amplification, neutrophil activation, and degranulation. These findings may provide novel targets for the precise treatment of patients with AMI.

Project description:Acute myocardial infarction (AMI) is the most serious type of coronary atherosclerotic diseases. The incidence of AMI in some countries increases year by year, and shows younger trend. Some study indicated that abnormal expression of lncRNAs was closely related to cardiovascular disease. The aim of this study was to examine the lncRNA expression profiles in peripheral blood mononuclear cells (PBMCs) of patients with AMI through controlled studies.In the present study, we examined the lncRNA and mRNA expression profiles in 8 patients with AMI, with 7 NCA (noncoronary artery) subjects as controls using RNA sequencing protocol (RNA-seq) on the Illumina HiSeq 4000 platform. The differentially expressed lncRNAs were selected for bioinformatic analysis including gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG). Quantitative real time PCR (qRT-PCR) was used to confirm the differential expression of lncRNAs.We kept about 11.29 gigabase (Gb) high-quality sequence data while the Q30 ranged from 94.39% to 95.19% for each sample. Compared to the lncRNA expression profiles of NCA controls, a total of 106 differentially expressed lncRNAs were discriminated in AMI patients, including 40 upregulated lncRNAs and 66 downregulated lncRNAs (P?<?.05). Among the genes corresponding to the identified mRNAs, 2905 genes are involved in biological processes, 339 in cellular components, and 501 in molecular functions. Based on the KEGG pathway analysis, the most enriched pathways corresponding to the differentially expressed lncRNAs were associated with systemic lupus erythematosus, alcoholism, oxidative phosphorylation, Parkinson's disease and viral carcinogenesis, and so on. Further, 3 upregulated and 3 downregulated lncRNAs were randomly selected for qRT-PCR verification and the results of qRT-PCR were consistent with the findings obtained from RNA sequencing analysis.As a result, differential expression profiles of lncRNAs in AMI were identified in our study. The results suggested that lncRNAs may play important roles in the biological and pathological processes of AMI. These findings may provide useful reference for the early diagnosis and risk stratification of AMI patients. To enlarge the sample size in the next step will be needed for further research to confirm our results.

Project description:ObjectivesMacrophage migration inhibitory factor (MIF), a pro-inflammatory cytokine, has been implicated in the pathogenesis of multiple inflammatory disorders. We determined changes in circulating MIF levels, explored the cellular source of MIF, and studied the role of MIF in mediating inflammatory responses following acute myocardial infarction (MI).Methods and resultsWe recruited 15 patients with MI, 10 patients with stable angina and 10 healthy volunteers and measured temporal changes of MIF in plasma. Expression of MIF, matrix metalloproteinase-9 (MMP-9) and interleukin-6 (IL-6) in cultured peripheral blood mononuclear cells (PBMCs) and the media were measured by ELISA or real-time PCR. Compared to controls, plasma levels of MIF and IL-6 were significantly elevated at admission and 72 h post-MI. In contrast, expression of MIF, MMP-9 and IL-6 by PBMCs from MI patients was unchanged at admission, but significantly increased at 72 h. Addition of MIF activated cultured PBMCs by upregulating expression of inflammatory molecules and also synergistically enhanced stimulatory action of IL-1? which were inhibited by anti-MIF interventions. In a mouse MI model we observed similar changes in circulating MIF as seen in patients, with reciprocal significant increases in plasma MIF and reduction of MIF content in the infarct myocardium at 3 h after MI. MIF content in the infarct myocardium was restored at 72 h post-MI and was associated with robust macrophage infiltration. Further, anti-MIF intervention significantly reduced inflammatory cell infiltration and expression of monocyte chemoattractant protein-1 at 24 h and incidence of cardiac rupture in mice post-MI.ConclusionMI leads to a rapid release of MIF from the myocardium into circulation. Subsequently MIF facilitates PBMC production of pro-inflammatory mediators and myocardial inflammatory infiltration. Attenuation of these events, and post-MI cardiac rupture, by anti-MIF interventions suggests that MIF could be a potential therapeutic target following MI.

Project description:Background: Acute myocardial infarction (AMI) can occur in patients with atherosclerotic disease, with or without plaque rupture. Previous studies have indicated a set of immune responses to plaque rupture. However, the specific circulating immune cell subsets that mediate inflammatory plaque rupture remain elusive. Methods: Ten AMI patients were enrolled in our study (five with and five without plaque rupture; plaque characteristics were identified by optical coherence tomography). By single-cell RNA sequencing, we analyzed the transcriptomic profile of peripheral blood mononuclear cells. Results: We identified 27 cell clusters among 82,550 cells, including monocytes, T cells, NK cells, B cells, megakaryocytes, and CD34+ cells. Classical and non-classical monocytes constitute the major inflammatory cell types, and pro-inflammatory genes such as CCL5, TLR7, and CX3CR1 were significantly upregulated in patients with plaque rupture, while the neutrophil activation and degranulation genes FPR2, MMP9, and CLEC4D were significantly expressed in the intermediate monocytes derived from patients without plaque rupture. We also found that CD4+ effector T cells may contribute to plaque rupture by producing a range of cytokines and inflammatory_x0002_related chemokines, while CD8+ effector T cells express more effector molecules in patients without plaque rupture, such as GZMB, GNLY, and PRF1, which may contribute to the progress of plaque erosion. Additionally, NK and B cells played a significant role in activating inflammatory cells and promoting chemokine production in the plaque rupture. Cell?cell communication elaborated characteristics in signaling pathways dominated by inflammatory activation of classical monocytes in patients with plaque rupture. Conclusions: Our studies demonstrate that the circulating immune cells of patients with plaque rupture exhibit highly pro-inflammatory characteristics, while plaque erosion is mainly associated with intermediate monocyte amplification, neutrophil activation, and degranulation. These findings may provide novel targets for the precise treatment of patients with AMI.

Project description:Polychlorinated biphenyls (PCBs) are well known carcinogenic persistent environmental pollutants and endocrine disruptors. Our aim was to identify the possible dysregulation of genes in PCB exposed peripheral blood mononuclear cells (PBMCs) in order to give more insight into the differential pathophysiological effects of PCB congeners and mixtures, with an emphasis on immunological effects and oxidative stress. The PBMCs of a healthy volunteer (male, 56 years old) were exposed to a mixture of dioxin-like (DL)-PCBs (PCB 77, 81, 105, 114, 118, 123, 126, 156, 157, 167, 169, and 189, 250 µg/L resp.) or non-dioxin-like (NDL)-PCBs (PCB 28, 52, 101, 138, 153, 180, 250 µg/L resp.) or single PCB congener (no.28, 138, 153, 180, 250 µg/L resp.). After an incubation period of 24 h, a microarray gene expression screening was performed, and the results were compared to gene expression in control samples (PBMCs treated with the vehicle iso-octane). Treatment of PBMCs with the DL-PCB mixture resulted in the largest number of differentially regulated genes (181 upregulated genes >2-fold, 173 downregulated >2-fold). Treatment with the NDL-PCB mix resulted in 32 upregulated genes >2-fold and 12 downregulated genes >2-fold. A gene set enrichment analysis (GSEA) on DL-PCB treated PBMCs resulted in an upregulation of 125 gene sets and a downregulation of 76 gene sets. Predominantly downregulated gene sets were involved in immunological pathways (such as response to virus, innate immune response, defense response). An upregulation of pathways related to oxidative stress could be observed for all PCB congeners except PCB-28; the latter congener dysregulated the least number of genes. Our experiment augments the information known about immunological and cellular stress responses following DL- as well as NDL-PCB exposure and provides new information on PCB 28. Further studies should be performed to evaluate how disruption of these pathways contributes to the development of autoimmune diseases and cancer.

Dataset Information

Altered gene expression pattern in peripheral blood mononuclear cells in patients with acute myocardial infarction.

Background

Methods and results

Conclusions

Publications

Altered gene expression pattern in peripheral blood mononuclear cells in patients with acute myocardial infarction.

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